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400 | 26,381,597 | Collectively they provided limited evidence that work skills programmes increase the likelihood of people with mental disorder who are offenders obtaining employment in the short term , but there are insufficient studies to determine the long-term impact of work skills programmes .
There is modest evidence to support inclusion of specific work skills programmes in the treatment of offenders with mental disorder . | BACKGROUND Academic literature and government initiatives have emphasised the importance of work as a means of improving health and reducing reoffending among offenders with mental disorders .
Whilst a number of work skills programmes have shown promise for offenders more generally , evaluation of evidence for their effectiveness for those with a mental disorder is lacking , particularly in relation to improving employment outcomes .
AIMS To assess the evidence on the effectiveness of work skills programmes for mentally disordered offenders . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The authors tested the hypothesis that early physical abuse is associated with later externalizing behavior outcomes and that this relation is mediated by the intervening development of biased social information-processing patterns . They assessed 584 r and omly selected boys and girls from European American and African American background s for the lifetime experience of physical abuse through clinical interviews with mothers prior to the child 's matriculation in kindergarten . Early abuse increased the risk of teacher-rated externalizing outcomes in Grade s 3 and 4 by fourfold , and this effect could not be accounted for by confounded ecological or child factors . Abuse was associated with later processing patterns ( encoding errors , hostile attributional biases , accessing of aggressive responses , and positive evaluations of aggression ) , which , in turn , predicted later externalizing outcomes With more than 200,000 veterans incarcerated , a significant need exists for the development of technologies that help veterans with felony histories return to employment . This study evaluated the effect of three methods of vocational assistance on competitive employment over a 6 mo follow-up period : ( 1 ) basic vocational services , ( 2 ) self- study using a vocational manual design ed for formerly incarcerated veterans , and ( 3 ) a group led by vocational staff using the vocational manual . We evaluated 111 veterans for time to obtain and total time of competitive employment . The group format was expected to be superior to the self- study and the self- study superior to basic services . Findings indicated that the group format was associated with quicker employment and more total employment than the basic and self- study conditions . Limitations and directions for future refinement are discussed Compared 11 probationers with a history of psychiatric referral to a r and omly selected group of unemployed persons from the State Unemployment Office in a number of job interview assessment situations . The probationers were rated as less skillful and also rated themselves as less likely to obtain employment than did the control Ss . After this pretest , the probationers were assigned to one of two treatment groups in which either monetary incentives for job interviews were provided or a skills training program was initiated . Posttest scores indicated that the skills program was most effective in changing behavioral and cognitive responses . These results generalized during the follow-up period ; the skills training group obtained employment more frequently than did the incentive group . Implication s for training critical skill deficits are discussed in terms of a response acquisition model BACKGROUND The value of the individual placement and support ( IPS ) programme in helping people with severe mental illness gain open employment is unknown in Europe . Our aim was to assess the effectiveness of IPS , and to examine whether its effect is modified by local labour markets and welfare systems . METHODS 312 patients with severe mental illness were r and omly assigned in six European centres to receive IPS ( n=156 ) or vocational services ( n=156 ) . Patients were followed up for 18 months . The primary outcome was the difference between the proportions of people entering competitive employment in the two groups . The heterogeneity of IPS effectiveness was explored with prospect i ve meta-analyses to establish the effect of local welfare systems and labour markets . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , with the number NCT00461318 . FINDINGS IPS was more effective than vocational services for every vocational outcome , with 85 ( 55 % ) patients assigned to IPS working for at least 1 day compared with 43 ( 28 % ) patients assigned to vocational services ( difference 26.9 % , 95 % CI 16.4 - 37.4 ) . Patients assigned to vocational services were significantly more likely to drop out of the service and to be readmitted to hospital than were those assigned to IPS ( drop-out 70 [ 45 % ] vs 20 [ 13 % ] ; difference -32.1 % [ 95 % CI -41.5 to -22.7 ] ; readmission 42 [ 31 % ] vs 28 [ 20 % ] ; difference -11.2 % [ -21.5 to -0.90 ] ) . Local unemployment rates accounted for a substantial amount of the heterogeneity in IPS effectiveness . INTERPRETATION Our demonstration of the effectiveness of IPS in widely differing labour market and welfare context s confirms this service to be an effective approach for vocational rehabilitation in mental health that deserves investment and further investigation |
401 | 27,357,126 | There is low quality evidence for live birth and moderate quality evidence for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer .
There was no evidence of a difference between the groups in cumulative pregnancy rates derived from fresh and frozen-thawed cycles following a single oocyte retrieval , but the evidence for this outcome was very low quality .
Thus , although there is a benefit favouring blastocyst transfer in fresh cycles , it remains unclear whether the day of transfer impacts on cumulative live birth and pregnancy rates . | BACKGROUND Advances in cell culture media have led to a shift in in vitro fertilisation ( IVF ) practice from cleavage stage embryo transfer to blastocyst stage transfer .
The rationale for blastocyst transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos , thus result ing in better live birth rates .
OBJECTIVES To determine whether blastocyst stage ( day 5 to 6 ) embryo transfers improve the live birth rate , and other associated outcomes , compared with cleavage stage ( day 2 to 3 ) embryo transfers . | OBJECTIVE To study and evaluate a sequential , extended embryo culture system . DESIGN Prospect i ve study . SETTING University-affiliated IVF clinic . PATIENT(S ) All couples who were treated between October 1997 and July 1998 . INTERVENTION(S ) A st and ard human tubal fluid plus 10 % serum substitute supplement ( SSS ) culture medium was used . The embryos were transferred to extended culture medium ( S2 or G2 ) on day 3 . MAIN OUTCOME MEASURE(S ) Blastocyst formation and implantation and pregnancy rates . RESULT ( S ) Forty percent of the 20 donated cryopreserved embryos progressed to the blastocyst stage by day 6 . Clinical ly , 7 ( 5.6 % ) of the 125 cycles did not result in a transfer . Blastocyst formation rates ranged from 33%-63 % in the five study groups . Implantation rates ranged from 15%-52 % and pregnancy rates ranged from 37%-75 % . CONCLUSION ( S ) Extended culture to day 5 or 6 results in acceptable blastocyst formation rates , implantation rates , and pregnancy rates The transfer of blastocysts has been associated with a very high implantation rate . However , not all embryos achieve the blastocyst stage . Our study was set up to demonstrate whether embryo morphology on day 3 predicts subsequent blastocyst formation . A prospect i ve study was carried out in 48 patients with a mean of 2.9 failed in-vitro fertilization ( IVF ) attempts . In this new cycle , the morphology of the embryos on day 3 was noted . After pre- selection of the embryos which would have been transferred on day 3 , all embryos were cultured individually and allowed to develop further until transfer on day 5 . The clinical pregnancy rate per transfer was 46 % , and the overall implantation rate was 24 % . When only blastocysts were transferred the pregnancy rate was 53 % with an implantation rate of 30 % . Thirty-nine per cent of all embryos reached the blastocyst stage on day 5 ; 47 % of class 1 and 2 embryos ( good quality ) in contrast to 21 % of class 3 and 4 embryos ( poor quality ) . Respectively 45 % of class 1 and 2 embryos and 69 % of class 3 and 4 embryos arrested in development or degenerated . Only 51 % of the embryos that were transferred on day 5 had been pre-selected for transfer on day 3 . In conclusion , it appears that the predictive value of embryo morphology on day 3 for subsequent blastocyst formation is limited Results of french multiple collaborative studies are reported to evaluate the possible benefits of coculture in human IVF program . Prospect i ve r and omized study of IVF with transfer on day two versus IVF with transfer on day 6 shows that coculture does not improve overall results but leads to a reduction of triple or quadruple pregnancies . When applied to patients with more than 4 failures of embryo transfers on day 2 , delayed transfer of blastocyst results in a high rate of clinical pregnancy ( 39 % ) . Transfers of frozen-thawed blastocysts result in 17.8 % ongoing pregnancies . Coculture is also a powerful tool for underst and ing early embryo development : when fertilization arises from sperm with poor characteristics or from frozen sperm of donor , embryo development appears to be altered : in these situations , rate of normally developing embryo is reduced and early embryo development becomes independent of fertilization rate BACKGROUND The aim of this study was to compare ongoing pregnancy rates per started cycle between patients r and omized at consultation to have embryo transfer either on day 3 or on day 5 of in-vitro culture . METHODS All patients < 43 years of age for whom IVF was indicated were allowed to participate in the study ( day 3 group , 234 patients ; day 5 group , 226 patients ) . Ovarian stimulation was performed either using GnRH antagonists/recombinant FSH ( rFSH ) ( day 3 , 70.1 % of patients ; day 5 , 72.6 % of patients ) or using the long GnRH agonist protocol /urinary gonadotropins ( day 3 , 29.9 % of patients ; day 5 27.4 % of patients ) . RESULTS The r and om decision to initiate a cycle leading to day 5 as compared with a day 3 transfer was associated with a significantly lower chance of embryo cryopreservation ( day 3 , 61.5 % ; day 5 , 50.4 % ; P<0.02 ) . Ongoing pregnancy rate per started cycle did not differ between the two groups compared [ day 3 , 32.1 % , 95 % confidence interval ( CI ) 26.4 - 38.2 % ; day 5 , 33.2 % , 95 % CI 27.3 - 39.5 % ] . CONCLUSIONS Advising patients at consultation to initiate an IVF cycle leading to a day 5 as compared with a day 3 transfer does not appear to increase the probability of ongoing pregnancy , and is associated with a significantly lower probability of obtaining cryopreserved embryos It is believed that delayed transfer of embryos after IVF allows for a better selection of good quality embryos . Hence , the number of embryos and all other prognostic factors being equal , transfer of day 3 embryos should be associated with higher implantation and pregnancy rates than transfer of day 2 embryos . To investigate this hypothesis , a prospect i ve r and omized study was carried out to compare implantation and pregnancy rates between day 2 and day 3 transfers . The relationship between the embryo quality score of day 2 and day 3 embryos and their respective implantation rates was also analysed . In a 2 year period all patients undergoing infertility treatment and in whom at least seven normally fertilized oocytes were obtained were included in the study . A minimization procedure was performed taking into account the patient 's age and the method of fertilization ( IVF or intracytoplasmic sperm injection ) . By using a uniform policy of embryo transfer , the number of embryos transferred was similar in both groups . The outcome parameters were embryo quality , implantation and pregnancy rates . No difference was observed in implantation and pregnancy rates between transfers on day 2 versus day 3 ( 23.8 versus 23.8 % and 47.9 versus 46.8 % respectively ) . The incidence of embryos of moderate to poor quality was higher in embryos cultured for 3 days compared with those cultured for 2 days . It is concluded that the outcomes of embryo transfer in terms of implantation and pregnancy rates are comparable for day 2 and day 3 embryos , although the overall embryo quality score decreases when embryos are kept in culture till day 3 BACKGROUND It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate . Therefore , advanced maternal age ( AMA ) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening ( PGD-AS ) on the outcome after assisted reproductive technology ( ART ) . METHODS A prospect i ve r and omized controlled clinical trial ( RCT ) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization ( FISH ) for the chromosomes X , Y , 13 , 16 , 18 , 21 and 22 in AMA couples ( aged > or = 37 years ) with a control group without PGD-AS . From the 400 ( 200 for PGD-AS and 200 controls ) couples that were allocated to the trial , an oocyte pick-up was performed effectively in 289 cycles ( 148 PGD-AS cycles and 141 control cycles ) . RESULTS Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls : 35.8 % ( 19.6 % ) [ % /per embryo transfer ( per cycle ) ] and 32.2 % ( 27.7 % ) , respectively ( NS ) . Significantly fewer embryos were transferred in the PGD-AS group than in the control group ( P<0.001 ) . The implantation rate ( with fetal heart beat ) was 17.1 % in the PGD-AS group versus 11.5 % in the control group ( not significant ; P=0.09 ) . We observed a normal diploid status in 36.8 % of the embryos . CONCLUSIONS This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred Preliminary results are presented concerning the first clinical application of cocultures of human embryos . In the experimental group , the embryos were cultured and transferred on day 5 post-insemination . Blastocyst formation was not dependent upon the stimulation regimen . Long term or ultrashort stimulation of the ovaries after gonadotrophin releasing hormone analogue gave 55 - 60 % blastocyst formation . Serum was not necessary to obtain blastocysts . When the embryos were cocultured , we observed an increase in the implantation rates per embryo in the pregnant patients . However , a real increase in the pregnancy rate per transfer was observed in a population of patients who had had repeated failures of embryo transfer . This observation is discussed as possibly bypassing an effect of uterine motility , but the overall beneficial effect has to be assessed in a double blind r and omized study . It is probable that improvements will not be observed for all the indications for in vitro fertilization OBJECTIVE To analyze the birth weights and sex ratio of infants born after blastocyst transfer . DESIGN Retrospective analysis . SETTING Three infertility clinics . PATIENT(S ) Patients admitted for IVF with blastocyst transfer . INTERVENTION None . MAIN OUTCOME MEASURE(S ) Birth weights and sex ratio of infants born after blastocyst transfer . RESULT ( S ) Statistically significantly more male infants were born after transfer of fresh blastocysts , either cocultured or cultured in sequential media . No specific differences in birth weight were observed between infants born after blastocyst transfer and those born after spontaneous conception . CONCLUSION ( S ) More male infants than female infants were born after blastocyst transfer when transfers were performed as soon as the blastocyst stage was reached and male embryos had a faster cleavage rate BACKGROUND Recently , advances in human IVF-embryo transfer ( ET ) have been reported using sequential media and blastocyst stage ET . In our previous report , using a prospect i ve , r and omized study , no advantage was found using the blastocyst stage ET compared with day 3 ET . This study was performed in order to evaluate implantation and pregnancy rates of hatching blastocyst stage ET compared with conventional day 3 ET . METHODS AND RESULTS A total of 480 patient cycles were evaluated using a prospect i ve , r and omized study . The pregnancy rate and implantation rate were compared between the day 3 ET ( n = 240 ) and hatching blastocyst stage ET ( Hat ET ; n = 240 ) . The Hat ET group had a pregnancy rate of 29.3 % ( 55 out of 188 ) and an implantation rate of 21.4 % ( 67 out of 313 ) . The day 3 ET group had a pregnancy rate of 29.2 % ( 70 out of 240 ) and an implantation rate of 19.1 % ( 93 out of 488 ) . In the Hat ET group , the pregnancy rate , implantation rate and ongoing pregnancy rate of day 5 ET and day 6 ET were all higher than the respective rates in the day 7 - 9 ET group . CONCLUSION We found that the pregnancy rate and implantation rate of ET with hatching stage blastocysts had no advantage compared with the conventional day 3 ET OBJECTIVE : To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer . STUDY DESIGN : A r and omized , prospect i ve study was conducted in Infertility clinic , Department of Obstetrics and Gynecology , Mahatma G and hi Hospital , Jaipur on 300 patients aged 25 - 40 years undergoing in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection ( ICSI ) cycle from May 2010-April 2011 . When three or more Grade -I embryos were observed on day 2 of culture , patients were divided r and omly into two study groups , cleavage stage transfer and blastocyst transfer group having 150 patients each . Primary outcomes evaluated were , Clinical pregnancy rate and Implantation rate . The results were analyzed using proportions , st and ard deviation and Chi-square test . RESULTS : Both the groups were similar for age , indication and number of embryos transferred . Clinical pregnancies after blastocyst transfer were significantly higher 66 ( 44.0 % ) compared to cleavage stage embryo transfer 44 ( 29.33 % ) ( P < 0.01 ) . Implantation rate for blastocyst transfer group was also significantly higher ( P < 0.001 ) . CONCLUSION : Blastocyst transfer having higher implantation rate and clinical pregnancy rate lead to reduction in multiple pregnancies OBJECTIVE To compare blastocyst-stage embryo transfers ( ETs ) with day 2 - 3 ETs in patients who failed to conceive in three or more day 2 - 3 IVF/ET cycles . DESIGN Prospect i ve , r and omized . SETTING Fertility unit in a university medical center . PATIENT(S ) Fifty-four patients with an adequate ovarian response underwent oocyte retrievals . The patients were prospect ively and r and omly divided into blastocyst-stage and day 2 - 3 ET groups . INTERVENTION(S ) Ovarian down-regulation was obtained using GnRH agonist , and controlled ovarian hyperstimulation was achieved using daily administration of gonadotropins . MAIN OUTCOME MEASURE(S ) The rate of blastocyst formation , ET cancellations , pregnancies , implantation , multiple gestation , and live births . RESULT ( S ) The clinical pregnancy rates per oocyte retrieval were 21.7 % and 12.9 % per blastocyst and day 2 - 3 ETs , respectively . Although there was a significantly higher implantation rate for blastocyst embryos ( 21.2 % ) as compared with 48- to 72-hour embryos ( 6 % ) , the multiple-pregnancy rate was not significantly different between both groups . An ET cancellation rate of 26 % and 6.4 % for blastocyst and day 2 - 3 ETs , respectively , was observed . The presence of two or more 8-cell embryos on day 3 in culture carried a high probability of obtaining blastocysts for transfer . CONCLUSION ( S ) This prospect i ve r and omized study suggests that in patients with an adequate ovarian response who failed to conceive in at least three IVF/ET cycles [ 1 ] . transfer of blastocyst-stage embryos carries a significantly higher implantation rate ; [ 2 ] . the pregnancy rate per oocyte retrieval and ET are higher in the blastocyst-stage group , even if it did not reach statistical significance ; [ 3 ] . a higher ET cancellation rate was observed in the whole blastocyst-stage group ; [ 4 ] . the ET cancellation rate was reduced significantly if the decision to proceed to blastocyst transfer was made on day 3 after oocyte retrieval , which is a post hoc conclusion BACKGROUND The respective advantages of day 3 and day 5 embryo transfer are a matter of debate . Previous comparisons did not include pronuclear stage zygote scoring and cumulative success rates ( fresh and cryopreserved embryos ) . METHODS Patients were r and omized prospect ively for day 3 or day 5 embryo transfer . Day 3 embryos were selected for transfer and cryopreservation by using combined evaluation at the pronuclear and cleavage stages . RESULTS There was no difference between day 3 and day 5 fresh embryo transfers as to the rates of pregnancy ( 58 versus 62 % ) , clinical pregnancy ( 56 versus 58 % ) , delivery ( 50 versus 48 % ) , implantation ( 35 versus 38 % ) and birth ( 33 versus 36 % ) rates . The corresponding values for cryopreserved embryo transfers were also similar . However , day 3 embryo transfer compared favourably with day 5 transfer when the pregnancy ( 90 versus 66 % ) , clinical pregnancy ( 85 versus 62 % ) and delivery ( 77 versus 52 % ) rates were calculated per oocyte recovery attempt . CONCLUSIONS With a selected population of good prognosis patients and our embryo selection criteria , the implantation potential of day 3 and day 5 embryos is equal . Per oocyte recovery attempt , day 3 transfer is more clinical ly efficient than day 5 transfer , but at least one transfer of cryopreserved embryos is necessary to manifest this superiority The effectiveness of blastocyst culture and transfer in human in-vitro fertilization ( IVF ) was evaluated in a prospect i ve r and omized trial in patients having a moderate to good response to gonadotrophin stimulation . Embryos were transferred either on day 3 after culture to around the 8-cell stage in Ham 's F-10 medium supplemented with fetal cord serum , or on day 5 after culture to the blastocyst stage in the sequential serum-free media G 1.2 and G 2.2 . The pregnancy rates after transfer on day 3 or day 5 were equivalent , 66 and 71 % respectively ; however , significantly more embryos were transferred on day 3 ( 3.7 ) than on day 5 ( 2.2 ) . The number of blastocysts transferred did not affect the implantation rate , and pregnancy rates when either two or three blastocysts were transferred were 68 and 87 % respectively . The implantation rate of the blastocysts ( 50.5 % fetal heart beat ) was significantly higher compared to the cleavage stage embryos transferred on day 3 ( 30.1 % ) . The percentage of blastocyst development was not affected by the number of 2-pronuclear embryos , or by maternal age . Irrespective of the number of blastocysts formed , pregnancy rates were similar . Furthermore , the pregnancy rate following blastocyst transfer in patients with 10 or more follicles at the time of human chorionic gonadotrophin administration was not affected by patient age . More than 60 % of patients having blastocyst culture and transfer had supernumerary embryos for cryopreservation . The establishment of a pregnancy following thaw and transfer confirmed the viability of cryopreserved blastocysts cultured in the absence of serum or co-culture . The ability to transfer just two blastocysts while maintaining high pregnancy rates will therefore help to eliminate high order multiple gestations and improve the overall efficiency of human IVF Transfer of embryos at the blastocyst stage has been associated with exceptionally high implantation rates . There are , however , only a few prospect i ve r and omized studies comparing day 3 versus day 5 embryo transfer . Furthermore , the number of embryos replaced in the day 3 group transfer is often higher than the number of blastocysts replaced , thereby affecting implantation rates . A total of 118 patients undergoing st and ard IVF/intracytoplasmic sperm injection who had developed at least three 8-cell embryos showing < 20 % extracellular fragmentation on day 3 were r and omized for day 3 or day 5 transfer . A maximum of two embryos were replaced . In this prospect i ve , r and omized study the implantation and pregnancy potential of embryos transferred on day 3 or day 5 were compared . Equal numbers of embryos were replaced in the two groups . There was no statistically significant difference between day 3 and day 5 transfer regarding positive human chorionic gonadotrophin rates ( 70 versus 67 % ) , clinical pregnancy rates ( 61 versus 51 % ) , implantation rates ( 44 versus 37 % ) , twinning rates ( 42 versus 41 % ) and rates of early pregnancy loss ( 15 versus 29 % ) . Transfer of embryos on day 3 or 5 showed similar implantation rates when equal numbers of embryos were transferred . Embryo transfer at the blastocyst stage seems to have no advantage over day 3 transfer in patients with more than two 8-cell embryos showing less than 20 % fragmentation on day 3 BACKGROUND This r and omized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates ( CPR ) per oocyte retrieval when compared with day 2 transfers . METHODS Blind r and omization for transfer on day 2 ( group 1 ) or day 5/6 ( group 2 ) was performed before stimulation . Oocytes and embryos were cultured in sequential media in 5.5 % CO(2 ) , 5 % O(2 ) , 89.5 % N(2 ) and 90 % humidity . A maximum of two embryos was transferred . RESULTS The two groups were similar for age , IVF indication , number of treatment cycles , rate of ICSI/IVF , number of fertilized oocytes and number of embryos transferred . The CPR/oocyte retrieval was comparable in group 1 ( 32 % ) and in group 2 ( 44 % ) , while the CPR/embryo transfer was significantly higher ( P < 0.01 ) in group 2 ( 60 % ) than in group 1 ( 35 % ) . Similarly , the implantation rate per embryo transferred was significantly higher ( P < 0.03 ) in group 2 ( 46 % ) than in group 1 ( 29 % ) . The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 ( 36.3 % ) and in group 1 ( 28.6 % ) . CONCLUSION This r and omized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers We have developed a coculture system with autologous human endometrial epithelial cells ( AEEC ) that retained many features of human endometrial epithelium . Implantation failure ( IF ; > 3 previous cycles failed with 3 - 4 good quality embryos transferred ) is a distressing condition in which 2-day embryo transfer repetition is the routine option . The objective of this study was to investigate the basics and to evaluate prospect ively the clinical value of embryo coculture on AEEC and blastocyst transfer with their own oocytes [ in vitro fertilization ( IVF ) patients ] or with donated oocytes ( oocyte donation patients ) compared to a routine day 2 embryo transfer for patients with IF . Scanning electron microscopy and mouse embryo assays demonstrate that EEC from fertile and IF patients were morphologically and functionally similar ; similar findings were observed in EEC obtained from fresh or frozen endometria . Clinical ly , 168 IVF cycles were performed in 127 patients with 3.8+/-0.2 previously failed cycles , and 80 cycles were performed in 57 patients undergoing oocyte donation with 3.0+/-0.2 previously failed cycles . Twenty IVF patients and 15 ovum donation patients with 3 previously failed cycles in whom a 2-day embryo transfer was performed were used as controls . In 88 % of ovum donation cycles , at least 2 blastocysts were available for transfer , with 60.1 % blastocyst formation ; 2.2+/-0.1 blastocysts were transferred/cycle , and 36 pregnancies ( determined by fetal cardiac activity ) were obtained ( 32.7 % implantation and 54.5 % pregnancy rates ) . In 168 IVF cycles , 8.1+/-0.2 embryos/cycle started coculture , result ing in 49.2 % blastocyst formation ; 2.3+/-0.2 blastocysts were transferred/cycle , and 29 clinical pregnancies were obtained ( 11.8 % implantation and 20.2 % pregnancy rates ) . Fifteen cycles were canceled ( 9 % ) . In oocyte donation patients with IF undergoing 2-day embryo transfer , implantation and pregnancy rates were significantly lower ( 4.5 % and 13.3 % ; P < 0.01 ) than with coculture ; however , in IVF patients with IF , results with day 2 transfer ( 10.7 % and 35 % ) were similar to those with coculture . The present study demonstrates that coculture of human embryos with AEEC and blastocyst transfer is safe , ethical , and effective and constitutes a new approach to improve implantation in patients with IF undergoing ovum donation , but not in IVF patients BACKGROUND The existence of a real benefit of blastocyst transfer is still a matter of debate . The aim of this study was to compare , in a prospect i ve r and omized trial , the outcome of day 2 and day 5 transfer of human embryos cultured in an ' in-house ' sequential medium . METHODS A total of 193 cycles from 171 patients with less than four previous IVF cycles , < 39 years old and with four or more zygotes on day 1 , were r and omly allocated to day 2 ( 94 cycles ) or day 5 ( 99 cycles ) transfer . Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a ' glucose-free ' cleavage medium . Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization . Two or three embryos were replaced according to the morphology . RESULTS A mean ( + /- SEM ) number of 2.1 + /- 0.4 and 1.9 + /- 0.3 embryos were replaced on day 2 and day 5 ( P < 0.001 ) respectively . Delivery rates per transfer were 44.1 and 37.1 % [ P = not significant ( NS ) ] , implantation rates were 31.4 and 29.4 % ( NS ) and multiple delivery rates 22 and 36 % ( NS ) for day 2 and day 5 groups respectively . Ten patients ( 10.1 % ) had no blastocysts available for transfer . CONCLUSIONS No clear benefits were observed using blastocyst transfer for patients aged < 39 years who had had less than four previous IVF cycle attempts High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome . This prompted us to quantify prospect ively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation , up to the time of blastocyst transfers , in 43 IVF-embryo transfer c and i date s. Contractility was assessed on the day of human chorionic gonadotrophin ( HCG ) administration , 4 days after HCG ( non-cavitating embryo transfer ; HCG + 4 ) , and 7 days after HCG ( blastocyst transfers ; HCG + 7 ) . For this , 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency . Our results indicated that a slight , yet significant , decrease in uterine contraction frequency , observed from the day of HCG ( 4.4 + /- 0.2 contractions/min ) to HCG + 4 ( 3.5 + 0.2 contractions/min ) , was followed by a more pronounced , additional decrease between HCG + 4 and HCG + 7 ( 1.5 + /- 0.2 contractions/min ; P < 0.001 ) . In conclusion , during the luteal phase of ovarian stimulation , uterine contractility decreases progressively , and reaches a nearly quiescent status 7 days after HCG administration , at the time of blastocyst transfers . It is possible that such a uterine relaxation assists blastocyst implantation BACKGROUND Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age . We design ed a prospect i ve , r and omized , controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage ( day 3 ) embryo and those undergoing transfer of a single blastocyst-stage ( day 5 ) embryo . METHODS We studied 351 infertile women under 36 years of age who were r and omly assigned to undergo transfer of either a single cleavage-stage embryo ( 176 patients ) or a single blastocyst-stage embryo ( 175 patients ) . Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone . RESULTS The study was terminated early after a prespecified interim analysis ( which included 50 percent of the planned number of patients ) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo ( P=0.02 ) . The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo ( 32.0 percent vs. 21.6 percent ; relative risk , 1.48 ; 95 percent confidence interval , 1.04 to 2.11 ) . Two multiple births occurred , both of monozygotic twins , both of which were in the group undergoing transfer of a single cleavage-stage embryo . CONCLUSIONS These findings support the transfer of a single blastocyst-stage ( day 5 ) embryo in infertile women under 36 years of age Purpose To determine if blastocyst transfer increases the ongoing and cumulative pregnancy rates , compared with day 3 embryo transfer , in women of all ages when at least 4 zygotes are obtained . Methods Prospect i ve study including patients undergoing a first IVF/ICSI treatment and assigned to cleavage stage ( n = 46 ) or blastocyst ( n = 58 ) embryo transfer . Supernumerary embryos were vitrified and patients failing to achieve an ongoing pregnancy after fresh embryo transfer would go through cryopreserved cycles . The main outcome measure was the ongoing pregnancy rate after the fresh IVF/ICSI transfer and the cumulative ongoing pregnancy rate . Results were also analyzed according to age ( under 35 and 35 or older ) . Results A majority of patients ( 96.6 % ) had a blastocyst transfer when at least 4 zygotes were obtained . The ongoing pregnancy rate was significantly higher in the day-5 group compared with the day-3 group ( 43.1 % vs. 24 % , p = 0.041 ) . The cumulative ongoing pregnancy rate was higher ( but not significantly ) with blastocyst than with cleavage stage embryos ( 56.8 % vs. 43.4 % , p = 0.174 ) . When analysed by age , patients 35 or older showed significantly higher ongoing pregnancy rate ( 48.4 % vs. 19.3 % , p = 0.016 ) and cumulative ongoing pregnancy rate ( 58 % vs. 25.8 % , p = 0.01 ) in the day-5 group compared to the day-3 group , while no such differences were observed in women under 35 . Conclusions Blastocyst transfer can be suggested whenever there are at least 4 zygotes . While there are no differences in women under 35 , the benefit of this option over cleavage stage transfer could be significant in women 35 or older OBJECTIVES To compare the implantation rate of embryos after 3 and 5 days of IVF culture . DESIGN Prospect i ve r and omization of ET depending on the weekday of ovum pick-up ( OPU ) . SETTING University Department of Endocrinology and Reproduction . PATIENTS All women entering an outclinic IVF program . INTERVENTIONS Two hundred thirty-three ETs performed on day 3 after OPU and 410 performed on day 5 were analyzed . When blastocysts with a clear inner cell mass were available , a maximum of two were replaced . RESULTS On day 3 after OPU , 60 pregnancies per 233 ET ( 26 % ) and on day 5 , 102 pregnancies per 410 ET ( 25 % ) were induced . The average implantation rate per embryo was 13 % and 12 % , respectively . After subdivision according to embryo morphology , pregnancy rate per ET ( n = 59 ) and implantation rate per embryo on day 3 with exclusively unfragmented embryos were 32 % and 18 % , respectively , not significantly different from ET ( n = 73 ) exclusively with embryos containing > 0 % and < 20 % fragments : 27 % and 12 % . After transfer on day 5 , when one or more cavitating embryos were available ( n = 227 ) , pregnancy and implantation rates were 40 % and 23 % , statistically different from ET on day 3 . On day 5 , ET exclusively with morula stages showing signs of starting blastulation ( n = 26 ) , pregnancy rate and implantation rate were 12 % and 11 % , respectively , from ET ( n = 157 ) with embryos not reaching the latter stage : 6 % and 3 % . CONCLUSIONS Overall ET results after 3 and 5 days are comparable . After 5 days of culture , one to two embryos can be replaced with an average implantation rate of > 23 % per embryo , minimizing the incidence of triplets OBJECTIVE To determine whether blastocyst transfer is of benefit to patients with multiple IVF failures . DESIGN Retrospective cohort study . SETTING The George Washington University Medical Center . PATIENT(S ) Patients undergoing IVF between October 1 , 1997 , and November 30 , 1998 , who had previously undergone three or more unsuccessful IVF cycles . Patients who had at least three embryos at the 8- to 12-cell stage available on day 3 were eligible for the study . INTERVENTION(S ) Patients were given the option of day 3 ET ( group A ) or blastocyst transfer ( group B ) . MAIN OUTCOME MEASURE(S ) Blastocyst-formation rate , clinical pregnancy rate ( PR ) per transfer , and implantation rate per transfer . RESULT ( S ) Groups A and B were similar in terms of age , the number of previous failed IVF cycles , fertilization rate , and the number of fertilized oocytes per cycle . The blastocyst-formation rate was 51.0 % . Clinical pregnancy and implantation rates per transfer were statistically significantly higher in the blastocyst-transfer group . There were no multiple pregnancies after blastocyst transfer . CONCLUSION Blastocyst transfer increases implantation rates and PRs in patients with multiple failed IVF cycles , without increasing the risk of multiple pregnancy INTRODUCTION In a r and omized controlled trial , we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good- quality embryos on day 3 . METHODS Multifollicular ovarian stimulation was performed with a GnRH agonist in 44 % of patients and with a GnRH antagonist in 56 % . Overall , 164 patients younger than 37 years fulfilled embryo quality criteria ( at least four having at least six cells on the morning of day 3 , maximum 20 % anucleate fragments ) on the third day of culture and were r and omized to the day 3 ( n = 84 ) or day 5 ( n = 80 ) groups . Equal numbers of embryos ( n = 2 ) were transferred in each group . RESULTS Demographics , stimulation parameters and embryological data were comparable in the two groups . Blastocyst-stage transfer result ed in a significantly higher ongoing pregnancy rate [ 51.3 versus 27.4 % ; odds ratio ( OR ) 2.78 , 95 % confidence interval ( CI ) 1.45 - 5.34 ] and live birth rate ( 47.5 versus 27.4 % ; OR 2.40 , 95 % CI 1.25 - 4.59 ) compared with day-3 embryo transfer . A high twin birth rate was observed in both groups ( 36.8 versus 30.4 % ; P > 0.05 ) . CONCLUSIONS A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer OBJECTIVE To compare in vitro fertilization ( IVF ) outcomes between fresh embryo transfer ( ET ) and frozen-thawed ET ( the " freeze-all " policy ) , with fresh ET performed only in cases without progesterone ( P ) elevation . DESIGN Prospect i ve , observational , cohort study . SETTING Private IVF center . PATIENT(S ) A total of 530 patients su bmi tted to controlled ovarian stimulation ( COS ) with a gonadotropin-releasing hormone-antagonist protocol , and cleavage-stage , day-3 ET . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Ongoing pregnancy rates . RESULT ( S ) A total of 530 cycles were included in the analysis : 351 in the fresh ET group ( when P levels were ≤1.5 ng/mL on the trigger day ) ; and 179 cycles in the freeze-all group ( ET performed after endometrial priming with estradiol valerate , at 6 mg/d , taken orally ) . For the fresh ET group vs. the freeze-all group , respectively , the implantation rate was 19.9 % and 26.5 % ; clinical pregnancy rate was 35.9 % and 46.4 % ; and ongoing pregnancy rate was 31.1 % and 39.7 % . CONCLUSION ( S ) The IVF outcomes were significantly better in the group using the freeze-all policy , compared with the group using fresh ET . These results suggest that even in a select group of patients that underwent fresh ET ( P levels ≤1.5 ng/mL ) , endometrial receptivity may have been impaired by COS , and outcomes may be improved by using the freeze-all policy Abstract Blastocyst transfer has been introduced as an alternative for improving the chance for in vitro fertilizations ( IVF ) implantation . The present study was to evaluate pregnancy rates when embryo transfer was performed either on day 2–3 ( cleavage stage ) or on day 4–5 ( blastocyst stage ) . This r and omized clinical trial included 118 infertile women . All the study subjects underwent controlled ovarian stimulation using a long protocol and r and omized into two groups . BS group ( n = 57 ) , the culture was extended to day 5 ( blastocyst stage ) and in the CS-group ( n = 61 ) , embryo culture was continued to day 3 ( cleavage stage ) . Ongoing pregnancies , abortion , implantation rate were evaluated . No significant differences were seen in the pregnancy rate between the two groups ( 33.3 % in the BS group versus 27.9 % in the CS group ; p = 0.519 ) . Abortion , implantation rate in two groups are not significant . Despite the lack of statistical difference between the two study groups , our data suggest that blastocyst transfer may be associated with a higher pregnancy and an overall better implantation rates . However , further studies with larger sample size are m and atory to confirm these findings . Chinese abstract 囊胚移植已经作为一种提高IVF植入机会的选择方法，本研究目的是评估在2 - 3天（卵裂期）移植或4 - 5天（囊胚期）移植的妊娠率。这个临床随机试验有118例不孕妇女。所有实验对象都采用长方案进行控制性卵巢刺激并随机分为两组。BS组(n=57)胚胎培养延长至5天（囊胚期），CS组(n=61)胚胎培养持续3天（卵裂期）。评估持续妊娠率、流产率、植入率。两组间妊娠率没有显著性差异(BS组为33.3 % ， CS组为27.9%，p=0.519)。两组间流产率和植入率无显著性差异。尽管两组之间没有明显统计学差异，数据提示囊泡期移植可能有更高的妊娠率和整体更好的植入率。但是需要进一步更大样本的研究来证实这些结果 OBJECTIVE To evaluate implantation and pregnancy rates in patients undergoing IVF after the transfer of a maximum of two embryos that had been cultured for 3 - 5 days . DESIGN Prospect i ve study . SETTING An IVF laboratory at a tertiary referral university hospital . PATIENT(S ) One thous and seven hundred eighty-seven couples who underwent their first IVF cycle between January 1995 and December 1997 . INTERVENTION(S ) In vitro fertilization and transfer of embryos after 3 , 4 , or 5 days of culture using a single medium without coculture . MAIN OUTCOME MEASURE(S ) Implantation and pregnancy rates . RESULT ( S ) Overall implantation and pregnancy rates were not significantly different with different culture periods . Forty-one percent of all available embryos developed into blastocysts on day 5 . The transfer of at least one good- quality blastocyst could be performed in 62 % of patients . Blastocysts had an implantation rate of 26 % per embryo , whereas the implantation rate of eight-cell embryos on day 3 was 18 % . Implantation rates for retarded , normal , and advanced embryos were not significantly different with an extended culture period . CONCLUSION ( S ) Under the study conditions , the transfer of embryos after 5 days rather than 3 days of embryo culture did not change the overall implantation and pregnancy rates . The implantation potential of embryos available for transfer can be assessed better after an extended culture period . Five days of culture allows the transfer of a reduced number of embryos without decreasing overall pregnancy rates OBJECTIVE To investigate whether the deleterious effect of E(2 ) on embryonic implantation is due to a direct effect on the endometrium , on the embryo , or both . DESIGN Prospect i ve , controlled in vitro study . SETTING Tertiary infertility center . PATIENT(S ) Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors ( n = 14 ) . INTERVENTION(S ) E(2 ) dose-response ( 0 , 10(-8 ) , 10(-7 ) , 10(-6 ) , 10(-5 ) , and 10(-4 ) M ) and time course ( day 2 vs. day 5 ) experiments were performed in an in vitro embryo adhesion assay composed of human polarized endometrial epithelial cells obtained from fertile patients and mouse embryos . MAIN OUTCOME MEASURE(S ) Blastocyst formation rate and embryo adhesion rate . RESULTS Monolayers of polarized endometrial epithelial cells expressed ERalpha at the mRNA level . The E(2 ) dose response of blastocysts with polarized endometrial epithelial cells ( n = 235 ) demonstrated a progressive reduction in embryonic adhesion that was statistically significant at 10(-6 ) M. When polarized endometrial epithelial cells were treated alone with increasing doses of E(2 ) for 3 days and E(2 ) was then removed and blastocysts added ( n = 410 ) , embryonic adhesion was not significantly reduced , except at 10(-4 ) M. When 2-day mouse embryos ( n = 609 ) were treated with increasing E(2 ) concentrations until day 5 , the rate of blastocyst formation significantly decreased at a concentration > or= 10(-6 ) M , and embryonic adhesion decreased when blastocysts ( n = 400 ) were obtained at a concentration > or= 10(-7 ) M. Time course experiments of embryos cultured for 2 days with polarized endometrial epithelial cells ( n = 426 ) showed that the adhesion rate was higher at E(2 ) levels of 10(-7 ) , 10(-6 ) and 10(-5 ) M compared with embryos cultured for 5 days ( n = 495 ) . CONCLUSION ( S ) High E(2 ) levels are deleterious to embryo adhesion in vitro , mainly because they have a direct toxic effect on the embryo that may occur at the cleavage stage OBJECTIVE To compare extended culture with blastocyst stage transfer and zygote intrafallopian transfer ( ZIFT ) in the management of IVF patients with repeated implantation failure . DESIGN Prospect i ve , nonr and omized study . SETTING An IVF unit at a university hospital . PATIENT(S ) Sixty-four infertile patients with more than three previous failed IVF-ET attempts . INTERVENTION(S ) Patients were allocated to undergo either blastocyst stage transfer ( Group 1 ; n = 32 ) or ZIFT ( Group 2 ; n = 32 ) . MAIN OUTCOME MEASURE(S ) Implantation , clinical pregnancy , and live birth rates . RESULT ( S ) Patient characteristics and response to stimulation were comparable for both groups . Totals of 84.3 % and 97 % of the patients underwent blastocyst transfer and ZIFT , respectively . Significantly more embryos were transferred through ZIFT ( 5.5+/-0.8 ) as compared with blastocyst transfer ( 2.3+/-1.4 ) , and there were significantly more cycles with embryo cryopreservation in the ZIFT group as compared to the blastocyst transfer group ( 15/32 vs. 4/32 , respectively ) . Implantation rate ( 13.6 % vs. 1.4 % ) , clinical pregnancy rate ( 40.6 % vs. 3.1 % ) , and live birth rates ( 38.7 % vs. 0 % ) were all significantly higher in the ZIFT group as compared to the blastocyst transfer group , respectively . CONCLUSION ( S ) Zygote intrafallopian transfer is a powerful clinical tool in the management of patients with RIF . In contrast , blastocyst stage transfer fails to improve the outcome in this poor-prognosis group . The pathophysiology of RIF should be the subject of intense investigation to allow the introduction of appropriate therapeutic measures earlier in the course of treatment Clinicians who treat unsuccessful couples despite repeated transfers of good quality embryos face a challenge . Among the various strategies that have been described , embryo transfer at the blastocyst stage has been postulated to improve implantation . A prospect i ve non-r and omized analysis was performed in 276 IVF patients who failed to conceive after at least two early embryo transfers of at least two grade 1 - 2 embryos per cycle . For the next attempt , couples chose between day 2 embryo transfer ( D2 group ; n = 147 ) and day 5/6 blastocyst transfer ( D5/D6 group ; n = 129 ) before starting the following attempt . Embryo quality was assessed and results were expressed as clinical pregnancy , live birth and implantation rates per cycle . Embryo grade 1 number was similar between both groups , whereas mean embryo score of the whole cohort was slightly higher in the D2 group . The live birth rates per cycle ( 27.9 versus 19.7 % ) and implantation rates per cycle ( 25.4 versus 12.4 % ) were higher in the D5/D6 group compared with the D2 group . Improved embryo selection and uterine receptivity may explain the additional benefit of embryo transfer at the blastocyst stage for couples with repeated implantation failures OBJECTIVE To evaluate the efficacy of blastocyst culture and transfer in human in vitro fertilization ( IVF ) as compared to day 3 embryo transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproduction unit . PATIENT(S ) A total of 162 IVF patients were included in the day 3 embryo transfer ( n = 82 ) and blastocyst transfer ( n = 80 ) groups . INTERVENTION(S ) Embryo transfer on day 3 after culture in the st and ard culture media and blastocyst transfer on day 5 or 6 after culture in the sequential culture media . MAIN OUTCOME MEASURE(S ) Implantation and pregnancy rates , multiple gestation rate . RESULT ( S ) The implantation rate for embryos transferred at the blastocyst stage was significantly higher than that for embryos transferred on day 3 ( 26 % vs. 13 % ) . The viable pregnancy rate was similar in both groups ( 29 % vs. 26 % ) . Significantly fewer embryos were required for transfer at the blastocyst stage compared with day 3 embryo transfer ( 2.0 + /- 0.1 vs. 3.5 + /- 0.63 ) . The high-order multiple gestation rate was significantly less with the blastocyst transfer than with the day 3 embryo transfer ( 4 % vs. 19 % ) . CONCLUSION ( S ) With the use of blastocyst culture , a few embryos can be transferred without decreasing the overall pregnancy rate . This may reduce multiple gestations and improve human IVF outcome To determine the best day for the selection and transfer of a single embryo , a prospect i ve , r and omized study was undertaken that compared the ongoing pregnancy rate ( PR ) after single embryo transfer ( SET ) on day 3 with that after single blastocyst transfer ( SBT ) on day 5 . Our results show an overall significantly higher PR after SBT ( 32.8 % ) compared with SET ( 23.2 % ) , and a PR of 40.8 % after SBT versus 25.6 % after excellent- quality embryos became available THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard Abstract Purpose : This study aim ed to evaluate the best day for embryo transfer in a prospect i ve unrestricted r and omized multicenter trial . Methods : Data were collected on a preformed Excel-sheet which contained r and om numbers from 1 to 5 for each subsequent patient as a preprogrammed day for embryo transfer . Information was requested on patient 's age , indication for sterility treatment , stimulation protocol used , numbers of oocytes retrieved , fertilized oocytes , cryopreserved embryos , and cell stage of embryos transferred . Results : A total of 329 embryo transfers were performed , result ing in 106 clinical pregnancies ( 32.2 % ) . Pregnancy rates achieved were 20.0 % on day 1 , 30.4 % on days 2 and 3 , and 50.0 % on days 4 and 5 ( p = 0.03 ) . Conclusions : Within the scope of the present r and omized multicenter trial , embryo transfers performed on days 4 and 5 enhanced the pregnancy rate significantly , compared to those of days 1 , 2 , and 3 OBJECTIVE To determine the efficacy of single blastocyst transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproductive technology unit . PATIENT(S ) Forty-eight women undergoing IVF-embryo transfer with day 3 FSH < or=10 mIU/mL and at least 10 follicles > 12 mm in diameter on day of hCG administration . INTERVENTION(S ) Embryo culture to the blastocyst stage in sequential media G1/G2 followed by transfer of either one or two blastocysts . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate , and twinning . RESULT ( S ) The transfer of a single blastocyst result ed in an implantation and ongoing pregnancy rate of 60.9 % with no twins . The transfer of two blastocysts result ed in an implantation rate of 56 % , an ongoing pregnancy rate of 76 % with a 47.4 % incidence of twins . CONCLUSION ( S ) Single blastocyst transfer is an effective method of eliminating multiple births while maintaining high pregnancy rates in this selected group of patients BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate . The aim of this study was to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospect i ve r and omized manner . Patients with four or more zygotes were r and omly allocated on day 1 to either day 3 or 5 transfers . Fertilization was achieved through regular IVF or intracytoplasmic sperm injection . Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers . The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups . Overall pregnancy rates per embryo transfer were the same ( 39 % ) in day 3 and 5 transfers . Implantation rates were 21 and 24 % for day 3 and 5 transfers respectively . The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes . The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers . Multiple gestation rate , number of abortions and ongoing pregnancies were similar in both groups . In conclusion , day 3 and 5 transfer had similar pregnancy , implantation and twinning rates . Currently , day 5 transfers have no advantages over day 3 transfers The transfer of blastocysts obtained by co-culture with ' Vero ' ( African green monkey kidney ) cells was offered to infertile couples with the following indications : ( i ) repeated failure of implantation , ( ii ) patients in whom multiple pregnancies had to be avoided ( malformed uterus or risk of descending uterus ) , ( iii ) patients where embryo development potential had to be assessed , and ( iv ) replacement of supernumerary embryos frozen at the blastocyst stage . In the 142 cycles analysed , the pregnancy rates per transfer were 37.2 , 36.3 , 13.0 and 13.6 % respectively for the couples with indications i-iv . The respective implantation rates per blastocyst were 20.0 , 16.7 , 7.1 and 9.3 % . In patients in whom multiple pregnancies had to be avoided , the transfer of a maximum of two blastocysts gave a pregnancy rate per cycle of 23.5 % , without any multiple pregnancies . The freezing of supernumerary embryos at the blastocyst stage allowed us to replace them using simple protocol s and to avoid cancellation of the transfer cycles . Embryo co-culture has been found to be an interesting technique for selected indications , making available a good number of blastocysts for transfer . The transfer of blastocysts allowed us to reduce the number of embryos transferred per patient and therefore also reduce the rate of multiple pregnancies ( there were no triplet pregnancies in this study ) . These results need to be confirmed by larger , r and omized studies with comparisons to control groups to evaluate the effectiveness of blastocyst transfers The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone ( GnRH ) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin ( HCG ) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI ( n=707 ) or IVF ( n=571 ) cycles , which had result ed in one or two blastocyst transfers . In GnRH antagonist cycles , cetrorelix acetate ( 3 mg ) was administered s.c . 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13 - 14 mm . LH support was provided by recombinant HCG ( 2.5 microg ) . Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores . The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol , although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups . Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients . Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support result ed in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles , although the embryo progression and blastulation parameters were comparable With the development of commercially available sequential media it is now possible to grow human embryos to the blastocyst stage without feeder cells . The transfer of blastocysts offers several advantages , the most important being synchronization of the embryos with the uterine endometrium and selection of the best quality embryos with a high implantation potential . This study was conducted to compare the efficiency of day 2 and day 5 transfer in a prospect i ve r and omized trial involving patients for whom embryo selection was possible ( i.e. those with more than three embryos on day 2 following insemination ) . We obtained equivalent clinical pregnancy rates per cycle for day 2 ( 41.7 % ) and day 5 ( 38.8 % ) transfer , but fewer embryos were transferred on day 5 ( 2.24 versus 3.03 ) . The implantation rates were 18.9 % on day 2 and 24.1 % on day 5 . Selected patients with a good response to gonadotrophins ( at least eight good quality metaphase II oocytes ) may therefore benefit from blastocyst transfer by a reduction in the multiple pregnancy rate , provided no more than two ( or even one ) blastocyst is transferred OBJECTIVE To compare the implantation and pregnancy rates after cleavage stage embryo transfer ( ET ) with transfer of blastocyst-stage ( days 5 - 6 ) embryos . STUDY DESIGN Prospect i ve r and omized trial at an assisted reproduction unit in a university hospital . Women with six or more follicles at the last ultrasound scan before oocyte aspiration were r and omized for transfer of a maximum of two embryos after 2 - 3 days ( n = 80 ) or after 5 - 6 days ( n = 64 ) of culture . Embryo quality , implantation and pregnancy rates were evaluated . Statistical significance was tested with the Chi-square test and Fisher 's exact test . RESULT ( S ) No significant difference was observed in implantation rates ( 21.1 % versus 20.9 % , respectively ) and clinical pregnancy rates ( 36.7 % versus 32.5 % respectively ) after blastocyst and cleavage stage transfers for the two groups . The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5 % per day 2 - 3 ET and 60 % per day 5 - 6 ET . CONCLUSION ( S ) The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different . Women who had at least one good quality blastocyst ( n = 25 ) had a high pregnancy rate ( 60 % per ET ) . Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination This prospect i ve , r and omized , controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin ( HCG ) undergoing intracytoplasmic sperm injection using the long protocol . A total of 200 women with oestradiol > 3000 pg/ml on the HCG day with four or more good- quality , day-3 embryos were r and omized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer . Clinical pregnancy rates ( CPR ; 41 % versus 59 % ; relative risk 0.70 , 95 % CI 0.52–0.93 ) and ongoing pregnancy/live-birth rates ( 35 % versus 52 % ; relative risk 0.67 , 95 % CI 0.46–0.93 ) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer . Using receiver operating characteristic curves , among women undergoing cleavage-stage embryo transfer , a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml , with lower CPR and ongoing pregnancy/live-birth rates ( P = 0.006 and 0.02 , respectively ) . No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer . Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG Extended embryo culture together with amelioration of embryo selection methods and embryo culture conditions have allowed a substantial increase on both pregnancy and implantation rates . However , uterine embryo transfers are still performed after 2 to 6 days of egg retrieval . In this paper , we show the results of two studies , one prospect i ve study comparing IVF outcome of day 2 and day 3 embryo transfers , and a retrospective study looking at blastocyst transfers versus day 3 embryo transfers in our egg donation program . Also , we test the predictive value of the presence of three or more seven cell-stage embryos on day 3 of development on blastocyst formation and pregnancy rates . No significant differences were found between day 2 and day 3 embryo transfers in terms of pregnancy , ongoing pregnancy , and implantation rates , as well as in multiple and in high order pregnancy . In general , day 6 embryo transfers result ed in significantly higher ongoing pregnancy and implantation rates compared with day 3 embryo transfers ( 41.1 per cent and 23.6 per cent versus 50.1 per cent and 38.1 per cent , respectively ) . No differences were found in terms of multiple gestations despite transferring significantly more embryos on day 3 compared with day 6 transfers . When less than three 7-cell embryos were present in the embryo cohort , day 6 embryo transfers did not improve the rates of ongoing pregnancy with regards to day 3 embryo transfer , although significant high implantation rates were obtained on the group of blastocyst transfer . The presence of three or more 7 cell-stage embryos improved significantly both ongoing pregnancy and rates on blastocyst transfers compared to day 3 embryo transfers ( 65.6 per cent versus 50.6 per cent and 37.4 per cent vs 24.7 per cent , respectively ) . In conclusion , at least in egg donation , day 3 embryo transfers do not improve either pregnancy or implantation rates when compared to day 2 transfers . Generally speaking blastocyst transfers give significantly higher chance of pregnancy and implantation rates per cycle and per transfer than early cleavage stage transfers . However , the absence of a good embryo cohort , that is having less than three 7 cell-stage embryos on day 3 , blastocyst transfers will improve implantation rates but not ongoing pregnancy rates BACKGROUND The aim of this study was to evaluate the effectiveness of the blastocyst culture method compared with the conventional day 3 transfer method using a prospect i ve trial . METHODS A total of 235 patients with 273 cycles were evaluated for a period of almost 1 year . Depending upon the sequence in which the ovum retrieval was performed , patients were prospect ively assigned ( alternate allocation ) to a culture period of 3 or 5 days duration . Embryos were transferred either on day 3 ( after culture in human tubal fluid ) or on day 5 ( after culture in sequential media ) . RESULTS The pregnancy rates after embryo transfer on days 3 and 5 were similar at 26.5 and 25.9 % respectively . Among the day 5 embryo transfer group , patients were divided into three groups corresponding to three sequential media . The pregnancy rates were 32.0 % using Irvine blastocyst medium , 6.9 % using G1.2/G2.2 and 32.4 % using Cook blastocyst medium . CONCLUSIONS The results of our study were not as successful as previous studies had been . Additionally , there may have been problems in day 5 embryo transfer , such as choosing the sequential media , quality control , contamination and so on . From the results of this study , it appears that day 5 embryo transfer has no advantages for ordinary patients of assisted reproductive technology |
402 | 26,666,384 | Consumption of highly salty foods and adherence to a Mediterranean dietary pattern can modulate the association between MC4R polymorphisms and the risk of obesity or Type 2 diabetes .
Despite the highly contradictory results of intervention studies , after short-term lifestyle interventions , children with variant alleles of MC4R single nucleotide polymorphisms can lose more body weight , compared with non-carriers , although they may have difficulty in maintaining this weight loss in the long-term .
The interaction between MC4R genes with dietary factors plays a significant role in the development of obesity or Type 2 diabetes phenotypes . | AIM To perform a systematic review of the effect of interaction between Melanocortin-4 receptor ( MC4R ) single nucleotide polymorphisms and diet on the development of obesity and Type 2 diabetes .
BACKGROUND Environmental factors , such as nutrient intakes or feeding behaviours , can modulate the association of polymorphism in the MC4R gene with obesity and Type 2 diabetes mellitus . | Bariatric surgery is the most effective long term weight-loss therapy for severe and morbidly obese patients . Melanocortin-4 Receptor ( MC4R ) mutations , the most frequent known cause of monogenic obesity , affect the regulation of energy homeostasis . The impact of such mutations on weight loss after bariatric surgery is still debated . The objective is to determine the impact of MC4R status on weight loss in obese subjects over one year after bariatric surgery . A total of 648 patients , who were referred to bariatric surgery in a single clinical nutrition department , were genotyped for their MC4R status . The following four groups were categorized : functional MC4R mutations , MC4R single nucleotide polymorphisms ( SNPs ) : Val103Ile ( V103L ) and Ile251Leu ( I251L ) , MC4R variant rs17782313 ( downstream of MC4R ) and MC4R SNP A-178C on the promoter . Each patient was matched with two r and omly paired controls without mutation . Matching factors were age , sex , baseline weight and type of surgery procedure ( Roux-en-Y gastric bypass and adjustable gastric b and ing ) . We compared weight loss between cases and controls at 3 , 6 and 12 months after surgery . Among 648 patients , we identified 9 carriers of functional MC4R mutations , 10 carriers of MC4R V103L and I251L SNPs , 7 carriers of the rs17792313 variant and 22 carriers of the A-178C SNP . Weight loss at 3 , 6 and 12 months did not differ between cases and controls , whatever the MC4R mutations . This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel Cigarette smoking impairs endothelial function and is one of the major risk factors for atherosclerosis and coronary heart disease . Insulin resistance is associated with major risk factors for atherosclerosis . We examined the effects of vitamin C on insulin sensitivity and endothelial function by measuring steady-state plasma glucose ( SSPG ) and flow-mediated dilation ( FMD ) of the brachial artery . We studied 16 current smokers with normal glucose tolerance , 15 nonsmokers with impaired glucose tolerance ( IGT ) , and 17 nonsmokers with normal glucose tolerance as controls . Both SSPG and FMD were blunted in smokers and nonsmokers with IGT compared with controls . In smokers , vitamin C decreased SSPG ( P < 0.01 by ANOVA ) with decreasing plasma thiobarbituric acid-reactive substances ( TBARS ) ( P < 0.05 by ANOVA ) and improved FMD ( P < 0.05 by ANOVA ) . Furthermore , vitamin C improved both SSPG ( P < 0.005 by ANOVA ) and FMD ( P < 0.05 by ANOVA ) in nonsmokers with IGT . SSPG , FMD , or TBARS in controls did not change after vitamin C infusion . There was a significant correlation between SSPG and FMD both in smokers and nonsmokers with IGT , whereas no correlation was observed in controls . In conclusion , both insulin sensitivity and endothelial function were impaired in smokers and nonsmokers with IGT and were improved by vitamin C. Thus increased reactive oxygen species play an important role in the pathogenesis of insulin resistance as well as endothelial dysfunction in smokers and nonsmokers with IGT AIM To evaluate the relation between type of dietary fatty acid and degree of insulin resistance . DESIGN A cross-sectional study . METHODS Anthropometrical data were measured in 538 subjects , aged 18 - 65 Years , selected r and omly from the municipal census of Pizarra ( Spain ) . An oral glucose tolerance test ( OGTT ) was given to all subjects and measurements were made of glycemia , insulinemia and the proportion of fatty acids in plasma phospholipids . Insulin resistance ( IR ) was estimated by homeostasis model assessment . Sample s of cooking oil being used were obtained from the kitchens . The strength of association between variables was measured by calculating the odds ratio ( OR ) from logistic models , and the relationships were measured by linear correlation coefficients . RESULTS Insulin resistance was significantly less in people who used olive oil compared with those who used sunflower oil or a mixture . Statistical significance remained in the group of people with normal OGTT after adjusting for obesity . In the whole sample , IR correlated negatively with the concentration of oleic acid ( r=-0.11 ; P=0.02 ) and positively with that of linoleic acid ( r=0.10 ; P=0.02 ) from the cooking oil . In subjects with normal OGTT , IR correlated negatively with oleic acid from cooking oil ( r=-0.17 ; P=0.004 ) and from plasma phospholipids ( r=-0.11 ; P=0.01 ) and positively with the concentration of linoleic acid in cooking oil ( r=0.18 ; P=0.004 ) and plasma phospholipids ( r=0.12 ; P=0.005 ) . The risk ( OR ) of having raised IR was significantly lower in people who consumed olive oil , either alone ( OR=0.50 ) or mixed ( OR=0.52 ) compared with those who consumed only sunflower oil . CONCLUSION There is an association between the intake of oleic acid , the composition of oleic acid in plasma phospholipids and peripheral insulin action Background Although the Fat Mass and Obesity ( FTO ) and Melanocortin-4 Receptor ( MC4R ) genes have been consistently associated with obesity risk , the association between the obesity-risk alleles with type 2 diabetes is still controversial . In some recent meta-analyses in which significant results have been reported , the associations disappeared after adjustment for body mass index ( BMI ) . However gene-diet interactions with dietary patterns have not been investigated . Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet ( MedDiet ) . Methods Case-control study in 7,052 high cardiovascular risk subjects ( 3,430 type 2 diabetes cases and 3,622 non-diabetic subjects ) with no differences in BMI . Diet was assessed by vali date d question naires . FTO-rs9939609 and MC4R-rs17782313 were determined . An aggregate genetic score was calculated to test additive effects . Gene-diet interactions were analyzed . Results Neither of the polymorphisms was associated with type 2 diabetes in the whole population . However , we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO- rs9939609 ( P-interaction=0.039 ) , the MC4R-rs17782313 ( P-interaction=0.009 ) and for their aggregate score ( P-interaction=0.006 ) . When adherence to the MedDiet was low , carriers of the variant alleles had higher type 2 diabetes risk ( OR=1.21 , 95%CI : 1.03 - 1.40 ; P=0.019 for FTO- rs9939609 and OR=1.17 , 95%CI:1.01 - 1.36 ; P=0.035 for MC4R-rs17782313 ) than wild-type subjects . However , when adherence to the MedDiet was high , these associations disappeared ( OR=0.97 , 95%CI : 0.85 - 1.16 ; P=0.673 for FTO- rs9939609 and OR=0.89 , 95%CI:0.78 - 1.02 ; P=0.097 for MC4R-rs17782313 ) . These gene-diet interactions remained significant even after adjustment for BMI . As MedDiet is rich in folate , we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects . However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern . Conclusions These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition The aim of the study was to analyze the phenotypic and epigenetic changes induced by the shift to a chow diet after an obesogenic environment . Animals were r and omized to fed chow ( control group ) or high-fat – sucrose diet ( HFS ) . After 10 weeks , half of the rats fed with HFS diet were reassigned to a chow diet ( rest group ) while the other half continued with the obesogenic diet ( HFS group ) until week 20 . Changes in fat content , biochemical profile , and DNA methylation levels of several gene promoters from retroperitoneal adipocytes were analyzed . HFS diet intake for 10 weeks induced obese phenotype in the animals , increasing body weight and fat content . These effects were maintained until the end of the trial in HFS group , where an increase in liver fat content , a modification of lipid profile , and retroperitoneal adipose tissue hypertrophy were also observed . Changing the dietary pattern reversed these parameters . Epigenetic analysis showed that HFS diet intake for 20 weeks hypermethylated several CpG sites ( 6.7 and 29.30 ) and hypomethylated CpG site 15 from leptin gene promoter . Moreover , the obesogenic diet also hypomethylated CpG site 1 from Fasn ( fatty acid synthase ) gene promoter , without changes on Ppargc1a ( peroxisome proliferator-activated receptor gamma coactivator 1-alpha ) , Srebf1 ( sterol regulatory element-binding transcription factor 1 ) , and aquaporin 7 . Shifting to a chow diet reverted HFS-induced DNA methylation levels of some CpG sites of leptin promoter . Changing the dietary pattern hypomethylated a CpG site of Srebf1 and hypermethylated other CpGs on Ppargc1a and Fasn promoter . This study shed light on the reversibility of phenotypical and epigenetic changes induced by a HFS diet intake Objective To assess associations and genotype × treatment interactions for melanocortin 4 receptor ( MC4R ) locus variants and obesity-related traits . Design and Methods Diabetes Prevention Program ( DPP ) participants ( N=3,819 , of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses ) were r and omized into intensive lifestyle modification ( diet , exercise , weight loss ) , metformin or placebo control . Adiposity was assessed in a subgroup ( n=909 ) using computed tomography . All analyses were adjusted for age , sex , ethnicity and treatment . Results The rs1943218 minor allele was nominally associated with short-term ( 6 month ; P=0.032 ) and long-term ( 2 year ; P=0.038 ) weight change . Eight SNPs modified response to treatment on short-term ( rs17066856 , rs9966412 , rs17066859 , rs8091237 , rs17066866 , rs7240064 ) or long-term ( rs12970134 , rs17066866 ) reduction in body weight , or diabetes incidence ( rs17066829 ) ( all Pinteraction < 0.05 ) . Conclusion This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial . One MC4R variant was directly associated with obesity-related traits or diabetes ; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions Because information on weight changes after lifestyle intervention in children with mutations in the melanocortin 4 receptor ( MC4R ) gene is scarce , we compared weight changes after lifestyle intervention between children with and without MC4R variations . A group of 514 overweight children ( aged 5 - 16 years ) , who presented to participate in a 1-year lifestyle intervention based on exercise , behavior , and nutrition therapy were screened for MC4R mutations . For comparison , children with MC4R mutations leading to reduced receptor function ( group A ) were each of them r and omly matched with five children of same age and gender without MC4R mutations ( group B ) . Changes of weight status were analyzed as change of BMI st and ard deviation scores ( BMI -SDSs ) . Furthermore , 16 children ( 3.1 % ) harbored MC4R mutations leading to reduced receptor function , and 17 ( 3.3 % ) children carried variations not leading to reduced receptor function . Children with and without MC4R mutations reduced their overweight at the end of intervention to a similar degree ( P = 0.318 between groups based on an intention-to-treat analysis ) . The maintenance of weight loss after intervention among children with MC4R mutations leading to reduced receptor function failed in contrast to children without such mutations ( P < 0.001 adjusted for BMI -SDS at baseline , age , and gender in an intention-to-treat analysis ) . In conclusion , children with MC4R mutations leading to reduced receptor function were able to lose weight in a lifestyle intervention but had much greater difficulties to maintain this weight loss supporting the impact of these mutations on weight status |
403 | 25,254,354 | The single study included in this review provides limited evidence on the effects of centre-based day care for children younger than five years of age in low- and middle-income countries . | BACKGROUND Because of poverty , children and families in low- and middle-income countries often face significant impediments to health and well-being .
Centre-based day care services may influence the development of children and the economic situation of parents by providing good quality early childhood care and by freeing parents to participate in the labour force .
OBJECTIVES To assess the effects of centre-based day care without additional interventions ( e.g. psychological or medical services , parent training ) on the development , health and well-being of children and families in low- and middle-income countries ( as defined by the World Bank 2011 ) . | Little is known about the long-term benefits of interventions that aim to promote early childhood development programs . The goal of this research was to determine whether an early childhood development intervention added to a nutrition intervention during preschool ages had lasting effects on the cognitive development of school-age children in communes of Thanh Hoa province in rural Vietnam . The study focused on a total of 313 children aged 6.5 - 8.5 y ( grade s 1 and 2 in primary school ) in 2 communes that were exposed to nutrition intervention or nutrition and early childhood development ( ECD ) intervention from 1999 to 2003 . Measurements of height and cognitive test scores ( Raven 's Progressive Matrices Test ) were collected from the children ; household characteristics were determined by interviews with mothers . Longitudinal analysis was performed by integrating the data with that collected from the same children in past surveys . Significant effects of the ECD intervention compared with the nutrition intervention were detected . The beneficial effect of ECD intervention on the cognitive test scores was large for the most nutritionally challenged children whose height-for-age Z-scores declined or remained in the stunted range . The findings help provide useful insights into the development of an effective integrated model of ECD and nutrition intervention for children in rural Vietnam The Cali Study involved the r and om assignment of 301 malnourished children to be exposed to one ( CT1 , n = 113 ) , two ( CT2 , n = 64 ) , three ( CT3 , n = 62 ) or four ( CT4 , n = 62 ) 9-mo periods of a multifocal day care-based intervention ( i.e. , education , health and nutrition ) . The ages at which the intervention was initiated for Groups CT4 , CT3 , CT2 and CT1 were 3.5 , 4.2 , 5.2 and 6.1 y , respectively . After the experimental phase , children were followed up in elementary school until they were 10.4 y old . Our secondary data analyses show that children who were exposed at an earlier age and for a longer period of time showed the highest degree ( P < or = 0.05 ) of improvement in weight and linear growth during the pre-school period . These improvements in physical growth could no longer be detected 3 y after the termination of the intervention OBJECTIVES We examined ( 1 ) whether attending out-of-home day care centres ( DCCs ) has differential effects on improvement of child nutrition and facilitation of maternal employment depending on availability of non-institutionalised childcare support and ( 2 ) whether attendance increases infectious diseases . METHODS In a prospect i ve before-after comparison study at public DCCs in Pokhara , Nepal , we compared weight-for-age Z-score ( WAZ ) and height-for-age Z-score ( HAZ ) among children attending DCCs between at admission , after 6 months , and after 1 year and determined differential changes in these measures between those with and without appropriate childcare support . We used repeated measures analysis of variance with interaction terms between support availability and DCC attendance . We compared maternal income and incidence of diarrhoea and fever in children between the periods of waiting and attending . RESULTS After 6 months , neither WAZ nor HAZ significantly changed . After 1 year , WAZ significantly improved , but HAZ did not change among all participants . Those without appropriate childcare support showed greater improvement in both WAZ and HAZ than those with support . While children were attending , income increased only among those mothers who were already working without any childcare support at baseline . Neither diarrhoea nor fever increased . CONCLUSIONS DCCs can be more beneficial for child nutrition and working mothers in households lacking childcare support than in those with support In the Abecedarian Project , a prospect i ve r and omized trial , the effects of early educational intervention on patterns of cognitive and academic development among poor , minority children were examined . Participants in the follow-up were 104 of the original 111 participants in the study ( 98 % African American ) . Early treatment was full-time , high- quality , educational child care from infancy to age 5 . Cognitive test scores collected between the ages of 3 and 21 years and academic test scores from 8 to 21 years were analyzed . Treated children , on average , attained higher scores on both cognitive and academic tests , with moderate to large treatment effect sizes observed through age 21 . Preschool cognitive gains accounted for a substantial portion of treatment differences in the development of reading and math skills . Intensive early childhood education can have long-lasting effects on cognitive and academic development Background This paper presents the study protocol for a pragmatic cluster r and omized controlled trial ( RCT ) with a supplementary matched control group . The aim of the trial is to evaluate a community-based early education and development program launched by the Government of Indonesia . The program was developed in collaboration with the World Bank with a total budget of US$ 127.7 million , and targets an estimated 738,000 children aged 0 to 6 years living in approximately 6,000 poor communities . The aim of the program is to increase access to early childhood services with the secondary aim of improving school readiness . Methods / Design The study is being conducted across nine districts . The baseline survey contained 310 villages , of which 100 were originally allocated to the intervention arm , 20 originally allocated to a 9-month delay staggered start , 100 originally allocated to an 18-month delay staggered start and 90 allocated to a matched control group ( no intervention ) . The study consists of two cohorts , one comprising children aged 12 to 23 months and the other comprising children aged 48 to 59 months at baseline . The data collection instruments include child observations and task/game-based assessment s as well as a question naire suite , village head question naire , service level question naires , household question naire , and child caretaker question naire . The baseline survey was conducted from March to April 2009 , midline was conducted from April to August 2010 and endline conducted early 2013 . The result ant participation rates at both the district and village levels were 90 % . At the child level , the participation rate was 99.92 % . The retention rate at the child level at midline was 99.67 % . Discussion This protocol paper provides a detailed record of the trial design including a discussion regarding difficulties faced with compliance to the r and omization , compliance to the dispersion schedule of community block grants , and procurement delays for baseline and midline data collection s. Considering the execution of the program and the result ant threats to the study , we discuss our analytical plan and intentions for endline data collection .Trials registration Current Controlled Trials IS RCT Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample To determine the risk for diarrheal disease ( DD ) in day-care centers ( DCC ) for children residing in a poor urban slum area of Quito , Ecuador , compared with that for children from the same environment but cared for in their own residential home ( RH ) , a prospect i ve age- , sex- and locale-controlled study of DD was conducted , including 115 children in DCC and 115 in RH , ages 12 to 42 months . The overall incidence of DD was 46/1000 child weeks . Diarrhea was more common in DCC than in RH ( relative risk ( RR ) , 1.75 ; 95 % confidence interval ( CI ) , 1.38 to 2.22 ; P < 0.001 ) . Poor hygienic practice s were more prevalent in DCC than in RH . The use of reused water for child h and washing before eating and for washing raw vegetables was associated with a higher risk of DD in DCC than in RH ( RR = 4.08 , CI 2.93 to 5.67 , P < 0.001 ; RR = 3.90 , CI 2.79 to 5.44 , P < 0.001 , respectively ) . These two practice s were risk factors in the DCC ( RR = 2.74 , CI 2.08 to 3.68 , P < 0.001 ; RR = 2.05 , CI 1.55 to 2.71 , P < 0.001 , respectively ) when compared with their absence in the same DCC . Shigella ( RR = 3.58 , CI 1.19 to 10.78 , P < 0.02 ) , Aeromonas ( RR = 10.47 , CI 1.35 to 81.05 , P < 0.01 ) , rotavirus ( RR = 2.86 , CI 1.87 to 4.39 , P < 0.001 ) and Giardia ( RR = 1.59 , CI 1.00 to 2.59 , P < 0.05 ) were more common in DCC than in RH . More than two-fifths of the Shigella and Aeromonas isolates were resistant to trimethoprim-sulfamethoxazole . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Methods to prevent two major mental disorders , schizophrenia and conduct disorder , have been elusive . This study assessed the effects of an early nutritional , educational , and physical exercise enrichment program on adult outcome for schizotypal personality , conduct disorder , and criminal behavior . METHOD Eighty-three children were assigned to an experimental enrichment program from ages 3 to 5 years and matched on temperament , nutritional , cognitive , autonomic , and demographic variables with 355 children who experienced usual community conditions ( control group ) . Both self-report and objective measures of schizotypal personality and antisocial behavior were obtained when the subjects were ages 17 and 23 years . RESULTS Subjects who participated in the enrichment program at ages 3 - 5 years had lower scores for schizotypal personality and antisocial behavior at age 17 years and for criminal behavior at age 23 years , compared with the control subjects . The beneficial effects of the intervention were greater for children who showed signs of malnutrition at age 3 years , particularly with respect to outcomes for schizotypy at ages 17 and 23 and for antisocial behavior at age 17 . CONCLUSIONS The results are consistent with an increasing body of knowledge that implicates an enriched , stimulating environment in beneficial psychological and behavioral outcomes . These findings have potential implication s for the prevention of schizophrenia and criminal behavior BACKGROUND School-based interventions involving teacher and /or child training have been shown to benefit teacher practice s and to prevent conduct problems and improve children 's social and emotional competence in developed countries ; however , we are aware of no reports from a developing country . We conducted a pilot study of the Incredible Years Teacher Training programme and a curriculum unit on social and emotional skills based on concepts and activities drawn from the Incredible Years Dina Dinosaur Classroom Curriculum to determine if this approach is appropriate for use with Jamaican pre-school teachers and children . METHODS Five pre-schools in Kingston , Jamaica were r and omly assigned to an intervention ( 3 pre-schools with 15 classrooms ) or control ( 2 pre-schools with 12 classrooms ) condition . Intervention involved seven whole-day teacher workshops using the Incredible Years Teacher Training programme supplemented by 14 child lessons in each class . The project was evaluated through structured observations of four categories of teacher behaviour and four observer ratings : two rating scales of child behaviour and two rating scales of classroom atmosphere . RESULTS Significant intervention benefits were found to teachers ' behaviour with increased positive behaviour [ b = 7.9 ; 95 % confidence interval ( CI ) : 3.5 , 12.3 ] , reduced negative behaviour ( b = -3.5 ; 95 % CI : -6.6 , -0.2 ) and increases in the extent to which teachers promoted children 's social and emotional skills ( b = 46.4 ; 95 % CI : 11.0 , 81.7 ) . The number of teacher comm and s was not significantly reduced ( b = -2.71 ; 95 % CI : -6.01 , 0.59 ) . Significant intervention benefits were found to ratings of child behaviour with an increase in children 's appropriate behaviour ( b = 5.7 , 95 % CI : 1.0 , 10.8 ) and in children 's interest and enthusiasm ( b = 7.2 , 95 % CI : 0.9 , 13.5 ) . Intervention also benefited classroom atmosphere with increases in opportunities provided for children to share and help each other ( b = 1.3 , 95 % CI : 0.5 , 2.1 ) and in teacher warmth ( b = 1.3 , 95 % CI : 0.9 , 1.8 ) . CONCLUSION This is a promising approach for improving the emotional climate of Jamaican pre-school classrooms and for improving child behaviour and participation OBJECTIVES The purpose of this study was to test whether early education intervention influences maternal employment , education , fertility , and receipt of public assistance and health insurance . METHODS The Infant Health and Development Program is a r and omized trial of the efficacy of early education on the outcomes of 985 low-birthweight , premature children . Families in eight sites received either pediatric follow-up and referral ( follow-up only group ) or pediatric services plus early intervention services ( intervention group ) for the first 3 years of the child 's life . RESULTS Mothers in the intervention group were employed more months and returned to the work force earlier than those in the follow-up only group . Fertility and education were not associated with treatment . Mothers who had some college education received more months of public assistance in the intervention group compared with the follow-up only group . Mothers who were employed received more public assistance and public health insurance in the intervention group compared with the follow-up only group , when maternal employment was controlled . CONCLUSIONS Findings are discussed in terms of the recent emphasis on two-generational programs directed to providing health , welfare , and child care services to young children and their families BACKGROUND The peak age prevalence of otitis media with effusion ( OME ) is in early childhood . Day care attendance has been established by various studies as a risk factor for the development of OME . OBJECTIVE This study is aim ed at evaluating the prevalence of OME among children aged 6 - 24 months , and the impact of day care center ( DCCs ) attendance on the OME occurrence . METHODS A prospect i ve cohort study conducted in children recruited from DCCs and immunization clinics in Surulere , Lagos state , Nigeria . They were matched mainly on their place of care , at home or at day care center and presence or absence of OME using pneumatic otoscopy and tympanometry . RESULTS A total of 152 children were studied . Based on their place of care , they were divided into day care attendees 64 ( 42.1 % ) , and non day care attendees 88 ( 57.9 % ) . The prevalence of OME was 37.7 % overall , 43.7 % in the day care attendees and 33.4 % in the non day care attendees . Factors found to positively influence the prevalence of OME in this study include : young age 6 - 12 months , female gender and day care attendance . CONCLUSION OME is common in Nigerian children at young age . Day care facility attendance significantly increased OME prevalence The Indian Integrated Child Development Services ( ICDS ) provides supplemental food to children aged 6 mo to 6 y. This study assessed the impact of enhancements to the existing Supplemental Nutrition Program of local production of supplemental food , home fortification with a micronutrient powder , and improved program monitoring . A quasi-experimental longitudinal design was used . Data were collected from 15 Anganwadi centers r and omly selected from the enhanced program and 15 from the usual program . Multilevel linear regression was used to examine changes over time between the 2 groups accounting for village-level variation in intent-to-treat analysis . Children in the enhanced program initially aged 12 - 18 mo gained 0.72 ( P = 0.02 ) greater height-for-age Z-score . Significant differences were observed in gain in weight-for-age Z-score among those initially aged 9 - 11 ( 2.48 ; P = 0.01 ) , 12 - 18 ( 0.76 ; P = 0.01 ) , and 19 - 24 mo old ( 0.73 ; P = 0.01 ) , and gain in weight-for-height Z-score among 9 - 11 ( 2.66 ; P = 0.04 ) and 19 - 24 mo old ( 0.99 ; P = 0.01 ) . For these age groups , the prevalence of stunting , underweight , or wasting averted ranged from 20.3 to 33.4 % . Energy intake in the enhanced program was significantly greater for boys initially aged 12 - 18 mo ( 575.1 kJ/d ; P = 0.03 ) . Results from a qualitative sub study supported the plausibility of observed outcomes . ICDS would be more effective in improving child nutrition if it included these enhancements . The enhancements studied may be useful in improving program delivery and uptake of other similar programs |
404 | 30,272,486 | No differences in survival or measures of dyspnea were observed in any of the studies .
No differences were noted in other adverse events .
Conclusions : Compared with chemical pleurodesis , IPC results in shorter hospital length of stay and fewer repeat pleural procedures but carries a higher risk of cellulitis . | Rationale : Several r and omized trials have compared the efficacy of an indwelling pleural catheter ( IPC ) versus the more traditional chemical pleurodesis in the management of malignant pleural effusion ( MPE ) .
Objectives : As part of the American Thoracic Society 's guidelines for management of MPE , we performed a systematic review and a meta‐ analysis to compare patient‐centered outcomes with the use of a tunneled pleural catheter versus chemical pleurodesis for the first‐line treatment of malignant pleural effusions . | 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 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 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 ) 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 BACKGROUND Patients with malignant pleural effusion ( MPE ) have limited prognoses . They require long-lasting symptom relief with minimal hospitalization . Indwelling pleural catheters ( IPCs ) and talc pleurodesis are approved treatments for MPE . Establishing the implication s of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment . Therefore , our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days ( from procedure to death or end of follow-up ) and safety . METHODS In this prospect i ve , 12-month , multicenter study , patients with MPE were treated with IPC or talc pleurodesis , based on patient choice . Key end points were hospital bed days from procedure to death ( total and effusion-related ) . Complications , including infection and protein depletion , were monitored longitudinally . RESULTS One hundred sixty patients with MPE were recruited , and 65 required definitive fluid control ; 34 chose IPCs and 31 pleurodesis . Total hospital bed days ( from any causes ) were significantly fewer in patients with IPCs ( median , 6.5 days ; interquartile range [ IQR ] = 3.75 - 13.0 vs pleurodesis , mean , 18.0 ; IQR , 8.0 - 26.0 ; P = .002 ) . Effusion-related hospital bed days were significantly fewer with IPCs ( median , 3.0 days ; IQR , 1.8 - 8.3 vs pleurodesis , median , 10.0 days ; IQR , 6.0 - 18.0 ; P < .001 ) . Patients with IPCs spent significantly fewer of their remaining days of life in hospital ( 8.0 % vs 11.2 % , P < .001 , χ(2 ) = 28.25 ) . Fewer patients with IPCs required further pleural procedures ( 13.5 % vs 32.3 % in pleurodesis group ) . There was no difference in rates of pleural infection ( P = .68 ) and protein ( P = .65 ) or albumin loss ( P = .22 ) . More patients treated with IPC reported immediate ( within 7 days ) improvements in quality of life and dyspnea . CONCLUSIONS Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis . Safety profiles and symptom control were comparable 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 |
405 | 31,750,249 | Subgroup analyses showed the predictive value of TMB was significant in non-small-cell lung cancer ( except for the OS ) and melanoma .
In addition , heterogeneity was substantial in targeted next generation sequencing group but tiny in whole exome sequencing group .
Furthermore , TMB and PD-L1 expression were capable to predict improved ORR of ICIs after stratification of each other , with tiny heterogeneity .
Moreover , tumor mutation burden and programmed cell death lig and 1 expression were independent factors on predicting efficacy of immune checkpoint inhibitors | Background : Despite an increasing underst and ing about tumor mutation burden ( TMB ) in cancer immunity and cancer immunotherapy , the comprehensive cognition between TMB and efficiency of immune checkpoint inhibitors ( ICIs ) is still lacking .
A systematic review and meta- analysis was conducted to evaluate the predictive value of TMB on efficacy of ICIs . | Pre clinical data suggest that combining a checkpoint inhibition with immunomodulatory derivative can increase anticancer response . We design ed a dose-escalation study using a 3 + 3 design to determine the safety , maximum tolerated dose ( MTD ) or recommended phase II dose ( R2PD ) and dose-limiting toxicities ( DLT ) of the anti – CTLA-4 antibody ipilimumab ( 1.5–3 mg/kg intravenously every 28 days × 4 ) and lenalidomide ( 10–25 mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity ) in advanced cancers . Total of 36 patients ( Hodgkin lymphoma , 7 ; melanoma , 5 ; leiomyosarcoma , 4 ; renal cancer , 3 ; thyroid cancer , 3 ; other cancers , 14 ; median of 3 prior therapies ) were enrolled . The MTD has not been reached and ipilimumab 3 mg/kg and lenalidomide 25 mg have been declared as R2PD . DLT were grade ( G ) 3 rash ( 3 patients ) and G3 pancreatitis ( 1 patient ) . G3/4 drug-related toxicities other than DLT were G3 anemia ( 5 patients ) , G3 thromboembolism ( 2 patients ) , G3 thrombocytopenia , G3 rash , G3 hypopituitarism , G3 pneumonitis , G3 transaminitis , and G4 hypopituitarism ( all in 1 patient ) . Eight patients had tumor shrinkage per immune-related response criteria ( −79 % to −2 % ) including a PR ( −79 % for 7.2 + months ) in a refractory Hodgkin lymphoma . Using comprehensive genomic profiling , a total mutation burden ( mutations/Mb ) was evaluated in 17 patients , with one of the patients achieving a PR demonstrated intermediate mutation burden . In conclusion , combination of ipilimumab and lenalidomide is well tolerated and demonstrated preliminary signals of activity in patients with refractory Hodgkin lymphoma and other advanced cancers . Mol Cancer Ther ; 17(3 ) ; 671–6 . © 2017 AACR The incidence of esophagogastric cancer is rapidly rising , but only a minority of patients derive durable benefit from current therapies . Chemotherapy as well as anti-HER2 and PD-1 antibodies are st and ard treatments . To identify predictive biomarkers of drug sensitivity and mechanisms of resistance , we implemented prospect i ve tumor sequencing of patients with metastatic esophagogastric cancer . There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy . Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy . The single Epstein-Barr virus-positive patient achieved a durable , complete response to immunotherapy . The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit . Selection for a tumor subclone lacking ERBB2 amplification , deletion of ERBB2 exon 16 , and comutations in the receptor tyrosine kinase , RAS , and PI3 K pathways were associated with intrinsic and /or acquired trastuzumab resistance . Prospect i ve genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance . Significance : Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer . This large prospect i ve analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers . Cancer Discov ; 8(1 ) ; 49 - 58 . © 2017 AACR.See related commentary by Sundar and Tan , p. 14See related article by Pectasides et al. , p. 37This article is highlighted in the In This Issue feature , p. 1 Purpose Alterations in DNA damage response and repair ( DDR ) genes are associated with increased mutation load and improved clinical outcomes in platinum-treated metastatic urothelial carcinoma . We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade . Methods Detailed demographic , treatment response , and long-term outcome data were collected on patients with metastatic urothelial carcinoma treated with atezolizumab or nivolumab who had targeted exon sequencing performed on pre-immunotherapy tumor specimens . Presence of DDR alterations was correlated with best objective response per Response Evaluation Criteria in Solid Tumors ( RECIST ) and progression-free and overall survival . Results Sixty patients with urothelial cancer enrolled in prospect i ve trials of anti-PD-1/PD-L1 antibodies met inclusion criteria . Any DDR and known or likely deleterious DDR mutations were identified in 28 ( 47 % ) and 15 ( 25 % ) patients , respectively . The presence of any DDR alteration was associated with a higher response rate ( 67.9 % v 18.8 % ; P < .001 ) . A higher response rate was observed in patients whose tumors harbored known or likely deleterious DDR alterations ( 80 % ) compared with DDR alterations of unknown significance ( 54 % ) and in those whose tumors were wild-type for DDR genes ( 19 % ; P < .001 ) . The correlation remained significant in multivariable analysis that included presence of visceral metastases . DDR alterations also were associated with longer progression-free and overall survival . Conclusion DDR alterations are independently associated with response to PD-1/PD-L1 blockade in patients with metastatic urothelial carcinoma . These observations warrant additional study , including prospect i ve validation and exploration of the interaction between tumor DDR alteration and other tumor/host biomarkers of immunotherapy response Background Inhibition of programmed death-lig and 1 ( PD-L1 ) with atezolizumab can induce durable clinical benefit ( DCB ) in patients with metastatic urothelial cancers , including complete remissions in patients with chemotherapy refractory disease . Although mutation load and PD-L1 immune cell ( IC ) staining have been associated with response , they lack sufficient sensitivity and specificity for clinical use . Thus , there is a need to evaluate the peripheral blood immune environment and to conduct detailed analyses of mutation load , predicted neoantigens , and immune cellular infiltration in tumors to enhance our underst and ing of the biologic underpinnings of response and resistance . Methods and findings The goals of this study were to ( 1 ) evaluate the association of mutation load and predicted neoantigen load with therapeutic benefit and ( 2 ) determine whether intratumoral and peripheral blood T cell receptor ( TCR ) clonality inform clinical outcomes in urothelial carcinoma treated with atezolizumab . We hypothesized that an elevated mutation load in combination with T cell clonal dominance among intratumoral lymphocytes prior to treatment or among peripheral T cells after treatment would be associated with effective tumor control upon treatment with anti-PD-L1 therapy . We performed whole exome sequencing ( WES ) , RNA sequencing ( RNA-seq ) , and T cell receptor sequencing ( TCR-seq ) of pretreatment tumor sample s as well as TCR-seq of matched , serially collected peripheral blood , collected before and after treatment with atezolizumab . These parameters were assessed for correlation with DCB ( defined as progression-free survival [ PFS ] > 6 months ) , PFS , and overall survival ( OS ) , both alone and in the context of clinical and intratumoral parameters known to be predictive of survival in this disease state . Patients with DCB displayed a higher proportion of tumor-infiltrating T lymphocytes ( TIL ) ( n = 24 , Mann-Whitney p = 0.047 ) . Pretreatment peripheral blood TCR clonality below the median was associated with improved PFS ( n = 29 , log-rank p = 0.048 ) and OS ( n = 29 , log-rank p = 0.011 ) . Patients with DCB also demonstrated more substantial expansion of tumor-associated TCR clones in the peripheral blood 3 weeks after starting treatment ( n = 22 , Mann-Whitney p = 0.022 ) . The combination of high pretreatment peripheral blood TCR clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical outcomes ( n = 10 , hazard ratio ( HR ) ( mean ) = 89.88 , HR ( median ) = 23.41 , 95 % CI [ 2.43 , 506.94 ] , p(HR > 1 ) = 0.0014 ) . Marked variations in mutation loads were seen with different somatic variant calling method ologies , which , in turn , impacted associations with clinical outcomes . Missense mutation load , predicted neoantigen load , and expressed neoantigen load did not demonstrate significant association with DCB ( n = 25 , Mann-Whitney p = 0.22 , n = 25 , Mann-Whitney p = 0.55 , and n = 25 , Mann-Whitney p = 0.29 , respectively ) . Instead , we found evidence of time-varying effects of somatic mutation load on PFS in this cohort ( n = 25 , p = 0.044 ) . A limitation of our study is its small sample size ( n = 29 ) , a subset of the patients treated on IMvigor 210 ( NCT02108652 ) . Given the number of exploratory analyses performed , we intend for these results to be hypothesis-generating . Conclusions These results demonstrate the complex nature of immune response to checkpoint blockade and the compelling need for greater interrogation and data integration of both host and tumor factors . Incorporating these variables in prospect i ve studies will facilitate identification and treatment of resistant patients BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer ( SCLC ) , but predictive markers are unknown . We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonr and omized or r and omized cohorts of CheckMate 032 . Patients received nivolumab ( 3 mg/kg every 2 weeks ) or nivolumab plus ipilimumab ( 1 mg/kg plus 3 mg/kg every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks ) . Efficacy of nivolumab ± ipilimumab was enhanced in patients with high tumor mutational burden . Nivolumab plus ipilimumab appeared to provide a greater clinical benefit than nivolumab monotherapy in the high tumor mutational burden tertile Although programmed death-lig and 1–programmed death 1 ( PD-L1–PD-1 ) inhibitors are broadly efficacious , improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden ( TMB ) . PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer ( NSCLC ) . However , obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging . Thus , an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy . Here , we describe a novel , technically robust , blood-based assay to measure TMB in plasma ( bTMB ) that is distinct from tissue-based approaches . Using a retrospective analysis of two large r and omized trials as test and validation studies , we show that bTMB reproducibly identifies patients who derive clinical ly significant improvements in progression-free survival from atezolizumab ( an anti-PD-L1 ) in second-line and higher NSCLC . Collectively , our data show that high bTMB is a clinical ly actionable biomarker for atezolizumab in NSCLC.A blood-based DNA sequencing assay to infer tumor mutational burden in the absence of tumor biopsy predicts response to PD-L1 blockade in patients with non-small-cell lung cancer Abstract Background Treatment with immune checkpoint blockade ( ICB ) with agents such as anti-programmed cell death protein 1 ( PD-1 ) , anti-programmed death-lig and 1 ( PD-L1 ) , and /or anti-cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer . Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection . Tumor mutation burden ( TMB ) is emerging as a potential biomarker . However , refinement of interpretation and context ualization is required . Material s and methods In this review , we outline the evolution of TMB as a biomarker in oncology , delineate how TMB can be applied in the clinic , discuss current limitations as a diagnostic test , and highlight mechanistic insights unveiled by the study of TMB . We review available data to date study ing TMB as a biomarker for response to ICB by tumor type , focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity . Results High TMB consistently selects for benefit with ICB therapy . In lung , bladder and head and neck cancers , the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing ( WES ) . PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies ; however , response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy . Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established . Conclusions TMB , in concert with PD-L1 expression , has been demonstrated to be a useful biomarker for ICB selection across some cancer types ; however , further prospect i ve validation studies are required . TMB determination by selected targeted panels has been correlated with WES . Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally . Key challenges will need to be addressed before broader use in different tumor types Background JS001 , a humanized IgG4 monoclonal antibody against the programmed death-1 ( PD-1 ) receptor , blocks the interaction of PD-1 with its lig and s and promotes T cell activation in pre clinical studies . This phase I study is design ed to evaluate the safety , tolerability , and clinical activity of JS001 in advanced melanoma or urologic cancer patients who are refractory to st and ard systemic therapy . Patients and methods In the dose escalation cohorts , subjects initially received a single-dose , intravenous infusion of JS001 , and were followed for 28 days followed by multi-dose infusions every 2 weeks . In the dose expansion cohorts , subjects received multi-dose infusions every 2 weeks . Clinical response was evaluated after each 8-week treatment cycle according to RECIST v1.1 criteria . Results Thirty-six subjects diagnosed with advanced melanoma ( n = 22 ) , urothelial cancer ( UC ) ( n = 8) , or renal cell cancer ( RCC ) ( n = 6 ) were enrolled . Melanoma subjects included 14 acral and 4 mucosal subtypes . JS001 was well tolerated , and no dose-limiting toxicity was observed . By the safety data cutoff date , 100 % of subjects had treatment-related adverse events ( TRAE ) with most adverse events being grade 1 or 2 , and ≥ grade 3 TRAEs occurred in 36 % . Among all 36 subjects , 1 confirmed complete response ( acral melanoma ) , 7 confirmed partial responses ( 2 acral melanoma , 1 mucosal melanoma , 2 UC , and 2 RCC ) , and 10 stable disease were observed , for an objective response rate of 22.2 % ( 95 % CI , 10.1 to 39.2 ) , and a disease control rate of 50.0 % ( 95 % CI , 32.9 to 67.1 ) . Clinical responses were correlated with PD-L1 expression on tumor cells , the presence of tumor infiltrating lymphocytes ( TIL ) , baseline tumor volume , ECOG performance status , serum LDH levels , high percentage of activated CD8 + T cells and CD3− CD16 + CD54 + NK cells in the peripheral blood as well as tumor mutational burden ( TMB ) . Conclusion JS001 was well tolerated and demonstrated promising anti-tumor activity in UC and RCC as well as in previously underexplored acral and mucosal melanoma subtypes . Subjects with an immune-active profile in the tumor microenvironment or in peripheral blood responded favorably to JS001 treatment . The completion of the current phase I study has led to the initiation of the first prospect i ve anti-PD-1 registration trial in Asia focusing on acral and mucosal melanoma subtypes , representative of the regional disease epidemiology . Trial registration Clinical Trial ID : NCT02836795 , registered July 19 , 2016 , retrospectively registered Order matters . Clinical outcomes were associated with the mutational and neoantigen loads , and T-cell infiltrates , of pretreatment sample s in a checkpoint blockade phase II trial only if nivolumab is used before ipilimumab , but not the reverse sequence . To underst and prognostic factors for outcome between differentially sequenced nivolumab and ipilimumab in a r and omized phase II trial , we measured T-cell infiltration and PD-L1 by IHC , T-cell repertoire metrics , and mutational load within the tumor . We used next-generation sequencing ( NGS ) and assessed the association of those parameters with response and overall survival . Immunosequencing of the T-cell receptor β-chain locus ( TCRβ ) from DNA of 91 pretreatment tumor sample s and an additional 22 pairs of matched pre- and posttreatment sample s from patients who received nivolumab followed by ipilimumab ( nivo/ipi ) , or the reverse ( ipi/nivo ) , was performed to measure T-cell clonality and fraction . Mutational and neoantigen load were also assessed by NGS in 82 of the 91 patients . Tumors were stained using IHC for PD-L1 + and CD8 + T cells . Pretreatment tumor TCR clonality and neoantigen load were marginally associated with best response with nivo/ipi ( P = 0.04 and 0.05 , respectively ) , but not with ipi/nivo . Amalgamated pretreatment mutational load and tumor T-cell fraction were significantly associated with best response with nivo/ipi ( P = 0.002 ) . Pretreatment PD-L1 staining intensity and CD8 + T-cell counts were correlated with T-cell fraction and clonality , but not mutational or neoantigen load . Patients with increased T-cell fraction posttreatment at week 13 had a 30-fold increased likelihood of survival ( P = 0.002 ) . Mutational and neoantigen load , and T-cell infiltrate within the tumor , were associated with outcome of sequential checkpoint inhibition using nivolumab then ipilimumab , but not when ipilimumab was administered before nivolumab Importance The anti – programmed cell death protein 1 ( PD-1 ) antibody pembrolizumab is approved by the US Food and Drug Administration for the treatment of microsatellite instability – high ( MSI-H ) or mismatch repair – deficient ( dMMR ) solid tumors , but the prevalence of MSI-H/dMMR prostate cancer and the clinical utility of immune checkpoint blockade in this disease subset are unknown . Objective To define the prevalence of MSI-H/dMMR prostate cancer and the clinical benefit of anti – PD-1/programmed cell death 1 lig and 1 ( PD-L1 ) therapy in this molecularly defined population . Design , Setting , and Participants In this case series , 1551 tumors from 1346 patients with prostate cancer undergoing treatment at Memorial Sloan Kettering Cancer Center were prospect ively analyzed using a targeted sequencing assay from January 1 , 2015 , through January 31 , 2018 . Patients had a diagnosis of prostate cancer and consented to tumor molecular profiling when a tumor biopsy was planned or archival tissue was available . For each patient , clinical outcomes were reported , with follow-up until May 31 , 2018 . Main Outcomes and Measures Tumor mutation burden and MSIsensor score , a quantitative measure of MSI , were calculated . Mutational signature analysis and immunohistochemistry for MMR protein expression were performed in select cases . Results Among the 1033 patients who had adequate tumor quality for MSIsensor analysis ( mean [ SD ] age , 65.6 [ 9.3 ] years ) , 32 ( 3.1 % ) had MSI-H/dMMR prostate cancer . Twenty-three of 1033 patients ( 2.2 % ) had tumors with high MSIsensor scores , and an additional 9 had indeterminate scores with evidence of dMMR . Seven of the 32 MSI-H/dMMR patients ( 21.9 % ) had a pathogenic germline mutation in a Lynch syndrome – associated gene . Six patients had more than 1 tumor analyzed , 2 of whom displayed an acquired MSI-H phenotype later in their disease course . Eleven patients with MSI-H/dMMR castration-resistant prostate cancer received anti – PD-1/PD-L1 therapy . Six of these ( 54.5 % ) had a greater than 50 % decline in prostate-specific antigen levels , 4 of whom had radiographic responses . As of May 2018 , 5 of the 6 responders ( 5 of 11 total [ 45.5 % ] ) were still on therapy for as long as 89 weeks . Conclusions and Relevance The MSI-H/dMMR molecular phenotype is uncommon yet therapeutically meaningful in prostate cancer and can be somatically acquired during disease evolution . Given the potential for durable responses to anti – PD-1/PD-L1 therapy , these findings support the use of prospect i ve tumor sequencing to screen all patients with advanced prostate cancer for MSI-H/dMMR . Because not all patients with the MSI-H/dMMR phenotype respond , further studies should explore mechanisms of resistance Importance Tumor mutational burden ( TMB ) , as measured by whole-exome sequencing ( WES ) or a cancer gene panel ( CGP ) , is associated with immunotherapy responses . However , whether TMB estimated by circulating tumor DNA in blood ( bTMB ) is associated with clinical outcomes of immunotherapy remains to be explored . Objectives To explore the optimal gene panel size and algorithm to design a CGP for TMB estimation , evaluate the panel reliability , and further vali date the feasibility of bTMB as a clinical actionable biomarker for immunotherapy . Design , Setting , and Participants In this cohort study , a CGP named NCC-GP150 was design ed and virtually vali date d using The Cancer Genome Atlas data base . The correlation between bTMB estimated by NCC-GP150 and tissue TMB ( tTMB ) measured by WES was evaluated in matched blood and tissue sample s from 48 patients with advanced NSCLC . An independent cohort of 50 patients with advanced NSCLC was used to identify the utility of bTMB estimated by NCC-GP150 in distinguishing patients who would benefit from anti – programmed cell death 1 ( anti – PD-1 ) and anti – programmed cell death lig and 1 ( anti – PD-L1 ) therapy . The study was performed from July 19 , 2016 , to April 20 , 2018 . Main Outcomes and Measures Assessment of the Spearman correlation coefficient between bTMB estimated by NCC-GP150 and tTMB calculated by WES . Evaluation of the association of bTMB level with progression-free survival and response to anti – PD-1 and anti – PD-L1 therapy . Results This study used 2 independent cohorts of patients with NSCLC ( cohort 1 : 48 patients ; mean [ SD ] age , 60 [ 13 ] years ; 15 [ 31.2 % ] female ; cohort 2 : 50 patients ; mean [ SD ] age , 58 [ 8 ] years ; 15 [ 30.0 % ] female ) . A CGP , including 150 genes , demonstrated stable correlations with WES for TMB estimation ( median r2 = 0.91 ; interquartile range , 0.89 - 0.92 ) , especially when synonymous mutations were included ( median r2 = 0.92 ; interquartile range , 0.91 - 0.93 ) , whereas TMB estimated by the NCC-GP150 panel found higher correlations with TMB estimated by WES than most of the r and omly sample d 150-gene panels . Blood TMB estimated by NCC-GP150 correlated well with the matched tTMB calculated by WES ( Spearman correlation = 0.62 ) . In the anti – PD-1 and anti – PD-L1 treatment cohort , a bTMB of 6 or higher was associated with superior progression-free survival ( hazard ratio , 0.39 ; 95 % CI , 0.18 - 0.84 ; log-rank P = .01 ) and objective response rates ( bTMB ≥6 : 39.3 % ; 95 % CI , 23.9%-56.5 % ; bTMB < 6 : 9.1 % ; 95 % CI , 1.6%-25.9 % ; P = .02 ) . Conclusions and Relevance The findings suggest that established NCC-GP150 with an optimized gene panel size and algorithm is feasible for bTMB estimation , which may serve as a potential biomarker of clinical benefit in patients with NSCLC treated with anti – PD-1 and anti – PD-L1 agents ABSTRACT Background : Although immunosenescence-induced difference on overall immune function and immune cell subsets between younger and older population s has been well characterized , the potential effect of patients ’ age on the efficacy of immune checkpoint inhibitors ( ICIs ) remains little known . We performed a meta- analysis to investigate whether age differences play a role in cancer immunotherapy efficacy based on a large amount of clinical data . Methods : We conducted a systematic search of PubMed , Embase and MEDLINE for relevant r and omized controlled trials . The primary outcome was overall survival ( OS ) and progression-free survival ( PFS ) was secondary outcome . The interaction test was used to assess the heterogeneity of HR between younger and older groups . Results : In total , 19 clinical r and omized trials involving 11157 patients were included . The pooled HR for OS was 0.73 ( 95 % CI 0.69–0.78 ) and 0.63 ( 95 % CI 0.52–0.73 ) for PFS in younger patients receiving ICIs treatments , when compared with younger patients treated with controls . For older patients treated with ICIs , the pooled HR for OS compared with controls was 0.64 ( 95 % CI 0.59–0.69 ) and 0.66 ( 95 % CI 0.58–0.74 ) for PFS . The difference on OS efficacy between younger and older patients treated with ICIs was significant ( Pheterogeneity = 0.025 ) . Conclusions : Immune checkpoint inhibitors significantly improved OS and PFS in both younger and older patients compared with controls , but the magnitude of benefit was clinical ly age-dependent . Patients ≥65 y can benefit more from immunotherapy than younger patients . Future research should take age difference into consideration in trials and focus on tolerance and toxicity of ICIs in older patients BACKGROUND Panel-based estimates of Tumor Mutational Burden ( psTMB ) are increasingly replacing whole-exome-sequencing ( WES ) Tumor mutational burden as predictive biomarker of immune checkpoint blockade ( ICB ) . DESIGN A mathematical law describing psTMB variability was derived using a r and om mutation model and complemented by the contributions of non-r and omly mutated real-world cancer genomes and intratumoral heterogeneity through simulations in publicly available data sets . RESULTS The coefficient of variation ( CV ) of psTMB decreased inversely proportional with the square root of the panel size and the square root of the TMB level . In silico simulations of all major commercially available panels in the TCGA pan-cancer cohort confirmed the validity of this mathematical law and demonstrated that the CV was 35 % for TMB=10 muts/Mbp for the largest panels of size 1.1 - 1.4 Mbp . Accordingly , misclassification rates ( gold st and ard : WES ) to separate " TMBhigh " from " TMBlow " using a cut-point of 199 mutations were 10 - 12 % in TCGA-LUAD and 17 - 19 % in TCGA-LUSC . A novel three-tier psTMB classification scheme which accounts for the likelihood of misclassification is proposed . Analysis of two independent data sets revealed that small gene panels were poor predictors of ICB response . Moreover , we noted significant intratumoral variance of psTMB scores in the TRACERx 100 cohort and identified indel burden in subsets of TMB high cases . CONCLUSIONS A universal mathematical law describes accuracy limitations inherent to psTMB , which result in significant misclassification rates . This scenario can be controlled by two measures : i ) a panel design that is based on the mathematical law described herein : halving the CV requires a fourfold increase in panel size , ii ) a novel three-tier TMB classification scheme . Moreover , inclusion of indel burden can complement TMB reports . This work has significant implication s for panel design , TMB testing , clinical trials and patient management BACKGROUND Pre clinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 ( PD-1 ) pathway to evade immune detection . In classic Hodgkin 's lymphoma , alterations in chromosome 9p24.1 increase the abundance of the PD-1 lig and s , PD-L1 and PD-L2 , and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription ( STAT ) signaling . We hypothesized that nivolumab , a PD-1-blocking antibody , could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin 's lymphoma . METHODS In this ongoing study , 23 patients with relapsed or refractory Hodgkin 's lymphoma that had already been heavily treated received nivolumab ( at a dose of 3 mg per kilogram of body weight ) every 2 weeks until they had a complete response , tumor progression , or excessive toxic effects . Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 ( also called CD274 and PDCD1LG2 , respectively ) loci and PD-L1 and PD-L2 protein expression . RESULTS Of the 23 study patients , 78 % were enrolled in the study after a relapse following autologous stem-cell transplantation and 78 % after a relapse following the receipt of brentuximab vedotin . Drug-related adverse events of any grade and of grade 3 occurred in 78 % and 22 % of patients , respectively . An objective response was reported in 20 patients ( 87 % ) , including 17 % with a complete response and 70 % with a partial response ; the remaining 3 patients ( 13 % ) had stable disease . The rate of progression-free survival at 24 weeks was 86 % ; 11 patients were continuing to participate in the study . Reasons for discontinuation included stem-cell transplantation ( in 6 patients ) , disease progression ( in 4 patients ) , and drug toxicity ( in 2 patients ) . Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these lig and s. Reed-Sternberg cells showed nuclear positivity of phosphorylated STAT3 , indicative of active JAK-STAT signaling . CONCLUSIONS Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin 's lymphoma . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT01592370 . ) BACKGROUND Nivolumab , a programmed death 1 ( PD-1 ) checkpoint inhibitor , was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma . This r and omized , open-label , phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment . METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were r and omly assigned ( in a 1:1 ratio ) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily . The primary end point was overall survival . The secondary end points included the objective response rate and safety . RESULTS The median overall survival was 25.0 months ( 95 % confidence interval [ CI ] , 21.8 to not estimable ) with nivolumab and 19.6 months ( 95 % CI , 17.6 to 23.1 ) with everolimus . The hazard ratio for death with nivolumab versus everolimus was 0.73 ( 98.5 % CI , 0.57 to 0.93 ; P=0.002 ) , which met the prespecified criterion for superiority ( P≤0.0148 ) . The objective response rate was greater with nivolumab than with everolimus ( 25 % vs. 5 % ; odds ratio , 5.98 [ 95 % CI , 3.68 to 9.72 ] ; P<0.001 ) . The median progression-free survival was 4.6 months ( 95 % CI , 3.7 to 5.4 ) with nivolumab and 4.4 months ( 95 % CI , 3.7 to 5.5 ) with everolimus ( hazard ratio , 0.88 ; 95 % CI , 0.75 to 1.03 ; P=0.11 ) . Grade 3 or 4 treatment-related adverse events occurred in 19 % of the patients receiving nivolumab and in 37 % of the patients receiving everolimus ; the most common event with nivolumab was fatigue ( in 2 % of the patients ) , and the most common event with everolimus was anemia ( in 8 % ) . CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma , overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus . ( Funded by Bristol-Myers Squibb ; CheckMate 025 Clinical Trials.gov number , NCT01668784 . ) Background Patients with advanced urothelial carcinoma that progresses after platinum‐based chemotherapy have a poor prognosis and limited treatment options . Methods In this open‐label , international , phase 3 trial , we r and omly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum‐based chemotherapy to receive pembrolizumab ( a highly selective , humanized monoclonal IgG4κ isotype antibody against programmed death 1 [ PD‐1 ] ) at a dose of 200 mg every 3 weeks or the investigator 's choice of chemotherapy with paclitaxel , docetaxel , or vinflunine . The co primary end points were overall survival and progression‐free survival , which were assessed among all patients and among patients who had a tumor PD‐1 lig and ( PD‐L1 ) combined positive score ( the percentage of PD‐L1–expressing tumor and infiltrating immune cells relative to the total number of tumor cells ) of 10 % or more . Results The median overall survival in the total population was 10.3 months ( 95 % confidence interval [ CI ] , 8.0 to 11.8 ) in the pembrolizumab group , as compared with 7.4 months ( 95 % CI , 6.1 to 8.3 ) in the chemotherapy group ( hazard ratio for death , 0.73 ; 95 % CI , 0.59 to 0.91 ; P=0.002 ) . The median overall survival among patients who had a tumor PD‐L1 combined positive score of 10 % or more was 8.0 months ( 95 % CI , 5.0 to 12.3 ) in the pembrolizumab group , as compared with 5.2 months ( 95 % CI , 4.0 to 7.4 ) in the chemotherapy group ( hazard ratio , 0.57 ; 95 % CI , 0.37 to 0.88 ; P=0.005 ) . There was no significant between‐group difference in the duration of progression‐free survival in the total population ( hazard ratio for death or disease progression , 0.98 ; 95 % CI , 0.81 to 1.19 ; P=0.42 ) or among patients who had a tumor PD‐L1 combined positive score of 10 % or more ( hazard ratio , 0.89 ; 95 % CI , 0.61 to 1.28 ; P=0.24 ) . Fewer treatment‐related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group ( 60.9 % vs. 90.2 % ) ; there were also fewer events of grade 3 , 4 , or 5 severity reported in the pembrolizumab group than in the chemotherapy group ( 15.0 % vs. 49.4 % ) . Conclusions Pembrolizumab was associated with significantly longer overall survival ( by approximately 3 months ) and with a lower rate of treatment‐related adverse events than chemotherapy as second‐line therapy for platinum‐refractory advanced urothelial carcinoma . ( Funded by Merck ; KEYNOTE‐045 Clinical Trials.gov number , NCT02256436 . Predicting responses to immunotherapy Colon cancers with loss-of-function mutations in the mismatch repair ( MMR ) pathway have favorable responses to PD-1 blockade immunotherapy . In a phase 2 clinical trial , Le et al. showed that treatment success is not just limited to colon cancer ( see the Perspective by Goswami and Sharma ) . They found that a wide range of different cancer types with MMR deficiency also responded to PD-1 blockade . The trial included some patients with pancreatic cancer , which is one of the deadliest forms of cancer . The clinical trial is still ongoing , and around 20 % of patients have so far achieved a complete response . MMR deficiency appears to be a biomarker for predicting successful treatment outcomes for several solid tumors and indicates a new therapeutic option for patients harboring MMR-deficient cancers . Science , this issue p. 409 ; see also p. 358 A pan-cancer biomarker is identified that can predict successful response to cancer immunotherapy in human patients . The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations . In a proof-of-concept study , we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 ( PD-1 ) . We have now exp and ed this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair – deficient cancers across 12 different tumor types . Objective radiographic responses were observed in 53 % of patients , and complete responses were achieved in 21 % of patients . Responses were durable , with median progression-free survival and overall survival still not reached . Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor . These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair – deficient cancers make them sensitive to immune checkpoint blockade , regardless of the cancers ’ tissue of origin |
406 | 32,273,655 | [ Conclusion ] A number of compensatory patterns during movement was observed , with a direct influence on improvements in stability and postural control throughout daily life .
Intensive gait training at an early age appears to produce long-term improvements in this population . | [ Purpose ] To describe ( 1 ) the current knowledge on gait and postural control in individuals with Down syndrome in terms of spatiotemporal , kinematics and kinetics , and ( 2 ) relevant rehabilitation strategies . [ | This study investigated how newly walking toddlers with Down syndrome ( DS ) , after different treadmill interventions , adopted clearance strategies and modified anticipatory locomotor adjustment patterns to negotiate an obstacle in their travel path . Thirty infants with DS ( about 10 months of age ) were recruited and r and omly assigned to either a lower-intensity , generalized ( LG ) treadmill training group , or a higher-intensity , individualized ( HI ) treadmill training group . Thirteen in each group completed a one-year-gait follow-up after the treadmill intervention . Initially , both groups chose to either crawl or walk over an obstacle . However , walking over the obstacle became their preferred clearance strategy over the course of the gait follow-up even though the height of the obstacle increased from visit to visit . The HI group used the strategy of walking over the obstacle at a considerably higher percentage than the LG group within 6 months after the training . When approaching the obstacle , both groups started to show consistent anticipatory locomotor adjustments about 6 months after the training . Both groups decreased velocity , cadence and step length , and increased step width at the last three pre-obstacle steps . It was concluded that the retention of the HI training effects led the HI group to predominantly walk over an obstacle earlier than the LG group within 6 months after treadmill intervention , and the two groups produced similar anticipatory locomotor adjustments in the last three steps before negotiating the obstacle Intellectual disability affects all spheres of people 's lives who suffer from it . It lowers the level of intellectual functioning , often stigmatizes , characteristically changing features , and decreases motor performance . Unfortunately , modern medicine can not cure intellectual disability ; however , there is a chance to improve the quality of life of people with mental retardation by means of physical exercises and by enhancing coordination , the quality of gait and efficiency in performing everyday activities . This paper deals with observations of static balance in 40 young females and males with mild Down syndrome , out of which 20 were subjected to a three-month sensorimotor training programme . The participants performed exercises with rehabilitation balls and air pillows twice a week , and the remaining persons constituted a control group . The balance platform test conducted at the beginning of the experiment revealed that the level of static one-legged balance was similar in both groups . A significant difference was noted in the length of the path of the general centre of gravity ( COG ) and the time frame in which the vertical projection of COG remained within the 13 mm radius circle , between the result of the test conducted under visual control and with the eyes closed , both in the group of the participants performing exercises and the ones who did not do them . After the training sessions the results of both tests improved in the group of the persons subjected to the training programme , however differences between the groups were not statistically significant , apart from the comparison of the time of keeping COG within the 13 mm radius circle at the beginning and at the end of the experiment by the participants who were physically active . Our results lead to a conclusion that exercises with the use of unstable surfaces improve deep sensibility in people with mild mental retardation Objective : The aim of the study was to determine the effect of exercise training on strength and balance in children with Down ’s syndrome . Design : R and omized controlled trial . Setting : Rehabilitation school for special children . Subjects and intervention : Twenty-three children were r and omized to intervention and control group . The intervention group ( n = 12 ) underwent progressive resistive exercises for lower limbs and balance training for six weeks . The control group continued their regular activities followed at school . Outcome measure : A h and held dynamometer was used to measure the lower limb muscle strength . Balance was assessed by the balance subscale of Bruininks Oseretsky Test of Motor Proficiency ( BOTMP ) . Results : Following the training , the children in the intervention group showed a statistically significant improvement ( P < 0.05 ) in the lower limb strength of all the muscle groups assessed . The strength of knee extensors was 12.12 lbs in the control group versus 18.4 lbs in the experimental group ; in hip flexors it was 12.34 lbs in the control group versus 16.66 lbs in the experimental group post-intervention . The balance of the children also improved significantly with an improvement in scores of the balance subscale of BOTMP ( 19.50 in the experimental group versus 9.00 in the control group , P = 0.001 ) . Conclusion : This study suggests that a specific exercise training programme may improve the strength and balance in children with Down ’s Background Infants with Down syndrome ( DS ) have delayed walking and produce less-coordinated walking patterns . Objective The aim of this study was to investigate whether 2 treadmill interventions would have different influences on the development of joint kinematic patterns in infants with DS . Design Thirty infants with DS were r and omly assigned to a lower-intensity , generalized ( LG ) treadmill training group ( LG group ) or a higher-intensity , individualized ( HI ) treadmill training group ( HI group ) and trained until walking onset . Twenty-six participants ( 13 in each group ) completed a 1-year gait follow-up assessment . Methods During the gait follow-up assessment , reflective markers were placed bilaterally on the participants to measure the kinematic patterns of the hip , knee , and ankle joints . Both the timing and the magnitude of peak extension and flexion at the hip , knee , and ankle joints , as well as peak adduction and abduction at the hip joint , in the 2 groups were compared . Results Both the LG group and the HI group showed significantly advanced development of joint kinematics at the gait follow-up . In the HI group , peak ankle plantar flexion occurred at or before toe-off , and the duration of the forward thigh swing after toe-off increased . Limitations Joint kinematics in the lower extremities were evaluated in this study . It would be interesting to investigate the effect of treadmill interventions on kinematic patterns in the trunk and arm movement . Conclusions The timing of peak ankle plantar flexion ( before toe-off ) in the HI group implies further benefits from the HI intervention ; that is , the HI group may use mechanical energy transfer better at the end of stance and may show decreased hip muscle forces and moments during walking . It was concluded that the HI intervention can accelerate the development of joint kinematic patterns in infants with DS within 1 year after walking onset BACKGROUND Longer life expectancy is result ing in increasing numbers of elderly adults with mental retardation . In elderly adults with Down syndrome ( DS ) , the maintenance of muscle strength , endurance , and dynamic balance are important to ensure quality of life and functional independence . The objective of this study was to compare isokinetic leg strength and dynamic balance of aged mentally retarded individuals with DS ( n = 16 , mean age 63 ) before and after a treadmill walking program lasting 6 months in comparison with a nonwalking control group ( n = 10 ) with similar physical characteristics . METHODS Participants in the study undertook leg strength testing on a dynamometer . Parameters measured included peak torque , peak torque % body weight , and average power % body weight . A " timed get-up and go " functional test for dynamic balance was also analyzed and compared prior to and after the treadmill program . RESULTS Knee extension and flexion isokinetic strength in elderly individuals with DS showed significant improvement after 6 months of treadmill training . Dynamic balance performance was also significantly improved ( p < .05 ) . CONCLUSIONS Aged adults with DS can significantly improve muscle strength and balance by adopting suitable programs of treadmill walking The main objective of this study is to underst and the differences in equilibrium control between normal subjects and those with Down syndrome . A total of 54 subjects participated voluntarily , divided into control group and Down syndrome group . The equilibrium of the subjects was tested under two conditions : bipedal support with eyes open and closed . The signals were analyzed in a time and frequency domain . The statistical parameters selected ( i.e. , RMS distance , mean velocity , mean frequency and sway area ) to analyze the behavior of the center of pressures ( CoP ) are calculated employing the result of the combination of the time series data in both directions ( i.e. result ant distance ) . In order to calculate the frequency b and s produced by the displacements of the CoP , a Fast Fourier Transform of the data was performed . The group with Down syndrome showed poorer static equilibrium control than the control group in the time domain . In the frequency domain , we found differences between the groups in the distribution of energy in the frequency b and s analyzed . In addition , we observed the existence of an interaction effect of the group and the condition tested ( p<0.001 ) . These findings show that in the absence of visual information , the control group increases the energy at low frequencies , while the group with Down syndrome decreases it . Additionally , the lower amount of energy observed in this b and under the ' eyes closed ' condition may serve to identify abnormalities in the functioning of the vestibular apparatus of individuals with Down syndrome and /or difficulties experienced by these individuals in extracting relevant information from this route Objective : Compare the effects of treadmill training and training with overground walking ( both without partial weight support ) on motor skills in children with cerebral palsy . Design : R and omized controlled clinical trial . Setting : Physical therapy clinics . Subjects : Thirty-six children with cerebral palsy ( levels I – III of the Gross Motor Functional Classification System ) r and omly divided into two intervention groups . Interventions : Experimental group ( 17 children ) su bmi tted to treadmill training without partial weight support . Overground walking group ( 18 children ) su bmi tted to gait training on a fixed surface ( ground ) . Training was performed for seven consecutive weeks ( two sessions per week ) , with four subsequent weeks of follow-up . Results : Both groups demonstrated improvements on the 6-minute walk test ( experimental group from 227.4 SD 49.4 to 377.2 SD 93.0 ; overground walking group from 222.6 SD 42.6 to 268.0 SD 45.0 ) , timed up- and -go test ( experimental group from 14.3 SD 2.9 to 7.8 SD 2.2 ; overground walking group from 12.8 SD 2.2 to 10.5 SD 2.5 ) , Pediatric Evaluation Disability Inventory ( experimental group from 128.0 SD 19.9 to 139.0 SD 18.4 ; overground walking group from 120.8 SD 19.0 to 125.8 SD 12.2 ) , Gross Motor Function Measure-88 ( experimental group from 81.6 SD 8.7 to 93.0 SD 5.7 ; overground walking group from 77.3 SD 7.0 to 80.8 SD 7.2 ) , Berg Balance Scale ( experimental group from 34.9 SD 8.5 to 46.7 SD 7.6 ; overground walking group from 31.9 SD 7.0 to 35.7 SD 6.8 ) after treatment . The experimental group demonstrated greater improvements than the overground walking group both after treatment and during follow up ( p < 0.05 ) . Conclusion : Treadmill training proved more effective than training with overground walking regarding functional mobility , functional performance , gross motor function and functional balance in children with cerebral palsy Purpose . To assess postural control in individuals with Down syndrome . Method . Sixty young adults with Down syndrome were assessed and compared to 10 non-h and icapped young . The subjects were asked to stay on a force platform for 30 seconds . Postural control was evaluated in two conditions : open and closed eyes . The kinetic data carried out from the force platform ( i.e. , ground reaction forces and Center of Pression ( COP ) displacements ) were both evaluated in time domain and in frequency domain . Results . Patients with Down syndrome are characterized by instable postural control . In particular the data evaluation in frequency domain underlined for Down syndrome subjects versus control group an increase in frequency oscillation both in anterior-posterior and in medio-lateral direction , that are confirmed in time domain analysis only for medio-lateral direction . In DS no changes are evident between eyes open and eyes closed condition . Conclusion . This study finds that subjects with Down syndrome included in this research demonstrate that deficits in postural control system that may provide a partial explanation for function balance problems that are common in these subjects ABSTRACT PEDro is produced by the Centre for Evidence -Based Physiotherapy ( CEBP ) , located in Sydney , Australia . PEDro is intended to be used to gain “ rapid access to bibliographic details and abstract s of r and omized controlled trials , systematic review s and evidence -based clinical practice guidelines in physiotherapy.”1 This column will provide some background information on the data base , as well as cover the basics of search ing its content People suffering from Ehlers-Danlos syndrome ( EDS ) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission . The same condition is present in people suffering from Down syndrome ( DS ) even if their clumsy movements are due to cerebral and cognitive impairments . The aim of this study was to quantify the gait patterns of subjects with EDS and with DS using Gait Analysis ( GA ) . We quantified the gait strategy in 12 EDS individuals and in 16 participants with DS . Both pathological groups were compared to 20 age-matched healthy controls in terms of kinematics and kinetics . Results showed that DS individuals are characterized by a more compromised gait pattern than EDS participants , even if both groups are characterized by joint hypermobility . All the patients showed significant decreased of ankle stiffness probably due to congenital hypotonia and ligament laxity , while different values of hip stiffness . These findings help to eluci date the complex biomechanical changes due to joint hypermobility and may have a major role in the multidimensional evaluation and tailored management of these patients Children with Down ’s syndrome ( DS ) often have greater postural sway and delay in motor development . Muscle weakness and hypotonia , particularly of the lower extremities , are theorized to impair their overall physical health and ability to perform daily activities . Therefore , the aim of this study was to investigate the effects of isokinetic training on muscle strength and postural balance in children with DS . Thirty-one children with DS ranging in age from 9 to 12 years were assigned r and omly into two groups . The control group received the conventional physical therapy , whereas the study group received the same therapy as the control group in addition to the isokinetic training 3 days a week for 12 weeks . Measurement of stability indices using the Biodex Stability System as well as peak torque of knee flexors and extensors of both sides using the isokinetic dynamometer was performed before and after 12 weeks of the treatment program . Each group showed significant improvements in postural balance and peak torque of knee flexors and extensors ( P<0.05 ) , with significantly greater improvements observed in the study group compared with the control group ( P<0.05 ) . These outcomes indicated that participation in the isokinetic training program induced greater improvements in muscle strength and postural balance in children with DS |
407 | 32,295,114 | The most commonly recommended training programs are based on exercising pelvic floor muscles , as they seem to have the largest impact on sexual function .
Mind – body disciplines also helped in managing menopausal symptoms .
However , as far as the most traditional programs were concerned , aerobic exercises showed inconsistent results and resistance training did not seem to convey any benefits . | During the menopausal period , sexual dysfunction is associated with the development or worsening of psychological conditions , causing deterioration in women ’s mental health and quality of life .
This systematic review aims to investigate the effects of different exercise programs on sexual function and quality of sexual life related to menopausal symptoms . | PURPOSE The purpose of our study was to evaluate the effect of cognitive behavioral therapy ( CBT ) , physical exercise ( PE ) , and of these two interventions combined ( CBT/PE ) on menopausal symptoms ( primary outcome ) , body image , sexual functioning , psychological well-being , and health-related quality of life ( secondary outcomes ) in patients with breast cancer experiencing treatment-induced menopause . PATIENTS AND METHODS Patients with breast cancer reporting treatment-induced menopausal symptoms ( N=422 ) were r and omly assigned to CBT ( n=109 ) , PE ( n=104 ) , CBT/PE ( n=106 ) , or to a waiting list control group ( n=103 ) . Self-report question naires were completed at baseline , 12 weeks , and 6 months . Multilevel procedures were used to compare the intervention groups with the control group over time . RESULTS Compared with the control group , the intervention groups had a significant decrease in levels of endocrine symptoms ( Functional Assessment of Cancer Therapy-Endocrine Symptoms ; P<.001 ; effect size , 0.31 - 0.52 ) and urinary symptoms ( Bristol Female Lower Urinary Tract Symptoms Question naire ; P=.002 ; effect size , 0.29 - 0.33 ) , and they showed an improvement in physical functioning ( 36-Item Short Form Health Survey physical functioning subscale ; P=.002 ; effect size , 0.37 - 0.46 ) . The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats ( problem rating scale of the Hot Flush Rating Scale ; P<.001 ; effect size , 0.39 - 0.56 ) and an increase in sexual activity ( Sexual Activity Question naire habit subscale ; P=.027 ; effect size , 0.65 ) . Most of these effects were observed at both the 12-week and 6-month follow-ups . CONCLUSION CBT and PE can have salutary effects on endocrine symptoms and , to a lesser degree , on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause . Future work is needed to improve the design and the planning of these interventions to improve program adherence Sexual dysfunction is present the most important problem among menopausal women and thus counseling may have a major role for improving menopausal sexual state in this population . We aim ed to assess effects of counseling on sexual function of menopause women and their spouses . An interventional trial study was performed on 120 consecutive Iranian couples ( menopause women and their spouses ) who were resident in Hamadan , Iran in 2015 . The subjects were r and omly assigned to receive counseling service ( n = 60 ) or did not receive this service ( n = 60 ) . Couples were asked to complete a st and ardized vali date d question naire assessing sexual function and behaviors . The frequency of sexual intercourse was considerably increased following first and second counseling sessions compared with the time before counseling in former group , while sexually state was remained unchanged in those who not received these counseling . Furthermore , dyspareunia in interventional women with counseling was significantly reduced after the first and second counseling , whereas this complaint was not significantly removed in the control group within the study period . Also , unsuccessful intercourse was significantly decreased in men who received counseling sessions , while this parameter was remained unchanged in other men . In addition , talking with the partner about sexually and Satisfaction degree of wife ’s love was significantly improved in both men and women in interventional groups compared with the control groups . Active and structured counseling effectively improve sexual functions and behaviors in menopausal women and their spouses Although a large number of studies report the impact of daily exercise on many aspects of women 's health , none of them address the relationship between Pilates exercise and sexual function prospect ively . The aim of this study was to assess the effect of Pilates exercise on sexual function in healthy young women using a vali date d question naire . In total , 34 premenopausal healthy Turkish women aged between 20 and 50 years who had regular menstrual cycles and sexual relationships were included in the study . Women were asked to complete Beck Depression Inventory ( BDI ) and Female Sexual Function Index ( FSFI ) question naires . Question naires were completed before and after 12 weeks of Pilates exercise . Primary endpoints were changes in total and individual domain scores on the FSFI and BDI . After the 12-week Pilates intervention , BDI scores were decreased and all domains of the FSFI were significantly improved with mean ± SD total FSFI scores increasing from 25.9 ± 7.4 to 32.2 ± 3.6 ( p < .0001 ) . This is the first prospect i ve study that quantifies the improvement in sexual function of healthy women after a 12-week Pilates program . Our findings suggest that Pilates may improve sexual function in healthy women . However , further studies with a larger sample size are needed in this field OBJECTIVE To examine the effects of " Rusie Dutton " on health and quality of life in menopausal women . METHOD Menopausal women ( aged 45 - 59 ) were recruited and r and omly allocated to 2 groups . Rusie Dutton group ( n = 24 ) practice d Rusie Dutton conducted by Wat Pho Thai Traditional Massage School for 13 weeks . The control group ( n = 26 ) was assigned to a waiting list and received no intervention . BW , BMI , restingHR , BP , flexibility , VO2max , and MENQOL including vasomotor , physical , psychosocial and sexual domains were measured at the beginning and the end . A paired- sample t-test and independent sample t-test were used for statistical analysis . RESULTS Significant improvement was found in all variables within group ( p < .05 ) in Rusie Dutton group , and a significant difference between groups was found ( p < .05 ) in all variables except BW and BMI . Therefore , it is concluded that the traditional Thai exercise Rusie Dutton can promote health related physical fitness and QOL in menopausal women BACKGROUND Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health , but the mortality benefits of light activity and risk for sedentary time remain uncertain . OBJECTIVES Using accelerometer-based measures , we 1 ) described the mortality dose-response for sedentary time and light- and moderate-to-vigorous-intensity activity using restricted cubic splines , and 2 ) estimated the mortality benefits associated with replacing sedentary time with physical activity , accounting for total activity . DESIGN US adults ( n = 4840 ) from NHANES ( 2003 - 2006 ) wore an accelerometer for ≤7 d and were followed prospect ively for mortality . Proportional hazards models were used to estimate adjusted HRs and 95 % CIs for mortality associations with time spent sedentary and in light- and moderate-to-vigorous-intensity physical activity . Splines were used to graphically present behavior-mortality relation . Isotemporal models estimated replacement associations for sedentary time , and separate models were fit for low- ( < 5.8 h total activity/d ) and high-active participants to account for nonlinear associations . RESULTS Over a mean of 6.6 y , 700 deaths occurred . Compared with less-sedentary adults ( 6 sedentary h/d ) , those who spent 10 sedentary h/d had 29 % greater risk ( HR : 1.29 ; 95 % CI : 1.1 , 1.5 ) . Compared with those who did less light activity ( 3 h/d ) , those who did 5 h of light activity/d had 23 % lower risk ( HR : 0.77 ; 95 % CI : 0.6 , 1.0 ) . There was no association with mortality for sedentary time or light or moderate-to-vigorous activity in highly active adults . In less-active adults , replacing 1 h of sedentary time with either light- or moderate-to-vigorous-intensity activity was associated with 18 % and 42 % lower mortality , respectively . CONCLUSIONS Health promotion efforts for physical activity have mostly focused on moderate-to-vigorous activity . However , our findings derived from accelerometer-based measurements suggest that increasing light-intensity activity and reducing sedentary time are also important , particularly for inactive adults 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 : The relationship between vulvovaginal atrophy and female sexual dysfunction is unclear . We investigated this association among sexually active postmenopausal women . Design : The Menopause Epidemiology Study is a cross-sectional , population -based study of women 40 to 65 years old in the United States chosen from a source population selected by r and om digit dialing and probability sampling . We focused on sexually active postmenopausal women ( N = 1,480 ) for our analyses . Vulvovaginal atrophy was defined as one or more of the following : vaginal dryness , itching , irritation ; pain on urination ; or pain or bleeding on intercourse . The Arizona Sexual Experience Survey was used to define female sexual dysfunction . Sexual dysfunction subtypes for desire , arousal , and orgasm difficulties were individually scored . We evaluated demographic , behavioral , reproductive history , and medication covariates for effect modification and confounding . Multivariate logistic regression was used to assess the relationship between vulvovaginal atrophy and female sexual dysfunction . Results : The prevalence of vulvovaginal atrophy ( 57 % ) and female sexual dysfunction ( 55 % ) was high . Women with female sexual dysfunction were 3.84 times more likely to have vulvovaginal atrophy than women without female sexual dysfunction ( 95 % CI : 2.99 - 4.94 ) . Hot flashes modified the association between vulvovaginal atrophy and desire difficulty . Educational level modified the association between vulvovaginal atrophy and arousal difficulty . Parity modified the association between vulvovaginal atrophy and orgasm difficulty . Conclusions : This large population -based study provides evidence of an association between vulvovaginal atrophy and overall female sexual dysfunction and its subtypes . Therapies aim ing to reduce symptoms of one condition may also relieve symptoms of the other Objective . This study was design ed to determine the effects of different short-term exercise programs on menopausal symptoms , psychological health , and quality of life in postmenopausal women . Material and Methods . Forty-two women were chosen from volunteering postmenopausal women presenting to the Department of Obstetrics and Gynecology of Bayındır Hospital between March and December 2009 . The women aged 45–60 years and experiencing menopause naturally were included in the study . They were r and omly divided into aerobic ( n = 18 ) and resistance ( n = 18 ) exercise groups . The women exercised 3 days per week for 8 weeks under the supervision of a physiotherapist . Aerobic exercise training was performed through a bicycle ergometer . Before and after the training , lipid profiles were measured and menopausal symptoms , psychological health , depression , and the quality of life were assessed through question naires . Results . In both exercise groups , no significant changes in lipid profiles were observed . In the resistance exercise group , excluding the urogenital complaints , there were significant improvements in all subscales of Menopausal Rating Scale ( MRS ) . In the resistance exercise group , excluding the phobic anxiety , there were significant improvements in all subscales of The Symptom Checklist . Depression levels significantly decreased in both groups . Improvements were observed in all subscales of menopause-specific quality of life question naire in both groups except for sexual symptoms . Conclusion . Resistance exercise and aerobic exercise were found to have a positive impact on menopausal symptoms , psychological health , depression , and quality of life Objectives The purpose of this study was to evaluate the quality of life ( QOL ) in postmenopausal members and non-members of the elderly support association in Borujen city , Iran . Methods This study was a cross-sectional descriptive study being applied to the participants were postmenopausal women of over 55 years . Thus , 40 postmenopausal members of the elderly support association of Borujen city and 40 non-members were r and omly selected . The 36 item short-form health survey ( SF-36 ) , with the 4 psychological , social , physical-movement , and environmental domains , was completed . Data were analyzed using SPSS software . Results The mean total score of QOL of member of the association was significantly greater than non-members . Student 's t-test showed a significant relationship between QOL and membership of the association ( P < 0.05 ) . One-way analysis of variance ( ANOVA ) showed that the mean QOL of postmenopausal women , according to membership and marital status ( P < 0.01 ) , housing ( P < 0.01 ) , and underlying disease ( P < 0.01 ) , was statistically significant . Conclusions According to the results , supportive measures , such as increasing the participation of the elderly in public life through proper preparations to join them and membership in peer groups such as support associations and non-governmental organizations ( NGOs ) can be greatly effective in improving QOL . The results showed that the QOL of the participants was at a moderate level and membership in support associations for the elderly was effected on the QOL in postmenopausal women . Moreover , considering the importance of the elderly in the community Background : Exercise and supplementation with isoflavones are therapies used to prevent and treat climacteric symptoms . Aim : To verify the effects of 10 weeks of combined aerobic and resistance training and isoflavone supplementation on climacteric symptoms in postmenopausal women . Methods : A r and omised , double-blind , controlled clinical trial was performed . A total of 32 postmenopausal women , aged 54.4 ± 5.4 years , with a body mass index of 26.6 ± 3.0 kg/m2 and 5.6 ± 4.6 years after menopause , were r and omly assigned to groups : placebo and exercise ( PLA + EXE , n = 15 ) or 100 mg of isoflavone and exercise ( ISO + EXE , n = 17 ) . At the beginning and after 10 weeks of aerobic + resistance ( 20 min each , moderate intensity ) training , climacteric symptoms were evaluated using the Blatt – Kupperman Menopausal Index , Cervantes Scale and Menopause Rating Scale . ANCOVA was used for analysis between groups and at different times , with the covariate adjusted by the pre-value . The level of significance considered was p < 0.05 . Results : A reduction in climacteric symptoms was observed in both groups , without differences between the interventions . The reductions were 45 % and 50 % for the Blatt – Kupperman Menopausal Index , 41 % and 52 % for the MRS and 39 % and 39 % for the Cervantes Scale in the ISO + EXE and PLA + EXE groups , respectively . In the descriptive analysis of the Blatt – Kupperman Menopausal Index values , there was an increase in the absence of symptoms from 48−77 % in the ISO + EXE group and 24−58 % in the PLA + EXE group . Conclusions : A period of 10 weeks of combined training was effective in improving climacteric symptoms in post-menopausal women . However , isoflavone supplementation did not promote additional effects in improving symptoms Objective : We investigated the effectiveness and cost-effectiveness of pessary treatment compared with pelvic floor muscle training ( PFMT ) in women with pelvic organ prolapse over a 2-year period . Methods : R and omized controlled trial with women ( ≥55 y ) with symptomatic pelvic organ prolapse , identified by screening . Participants were recruited from 20 primary care practice s ( October 2009-December 2012 ) . Primary outcome was the difference in change of pelvic floor symptoms ( PFDI-20 score ) between groups over 24 months . Secondary outcomes included prolapse , urinary , and anorectal symptoms ; quality of life ; costs ; sexual functioning ; prolapse stage ; pelvic floor muscle function ; and participants ’ perceived symptom improvement . Results : There was a nonsignificant difference in the primary outcome between pessary treatment ( n = 82 ) and PFMT ( n = 80 ) with a mean difference of −3.7 points ( 95 % CI , −12.8 to 5.3 ; P = 0.42 ) in favor of pessary treatment . A significantly greater improvement in the prolapse symptom score was , however , seen with pessary treatment ( mean difference −3.2 points [ 95 % CI , −6.3 to −0.0 ; P = 0.05 ] ) . Direct medical costs over the 2-year study were $ 309 and $ 437 per person for pessary treatment and PFMT , respectively . Conclusions : In older women with symptomatic prolapse , there was no significant difference between pessary treatment and PFMT in reducing pelvic floor symptoms , but specific prolapse-related symptoms did improve more with pessary treatment . Pessary treatment was preferable in the cost-effectiveness analysis . When counseling women for prolapse treatment it should , however , be taken into account that pessary fitting fails in a considerable portion of women and that pessary treatment was associated with more side effects compared with PFMT BACKGROUND The sex lives of women are strongly affected by menopause . Non-pharmacologic approaches to improving the sexual function of postmenopausal women might prove effective . AIM To compare two methods of intervention ( formal sex education and Kegel exercises ) with routine postmenopausal care services in a r and omized clinical trial . METHODS A r and omized clinical trial was conducted of 145 postmenopausal women residing in Chalus and Noshahr , Iran . Their sexual function statuses were assessed using the Female Sexual Function Index ( FSFI ) question naire . After obtaining written informed consents , they were r and omly assigned to one of three groups : ( i ) formal sex education , ( ii ) Kegel exercises , or ( iii ) routine postmenopausal care . After 12 weeks , all participants completed the FSFI again . Analysis of covariance was used to compare the participants ' sexual function before and after the interventions , and multiple linear regression analysis was used to determine the predictive factors for variation in FSFI scores in the postintervention stage . OUTCOMES Sexual function was assessed using the FSFI . RESULTS There were no statistically significant differences in demographic and socioeconomic characteristics and FSFI total scores among the three study groups at the outset of the study . After 12 weeks , the scores of arousal in the formal sex education and Kegel groups were significantly higher compared with the control group ( 3.38 and 3.15 vs 2.77 , respectively ) . The scores of orgasm and satisfaction in the Kegel group were significantly higher compared with the control group ( 4.43 and 4.88 vs 3.95 and 4.39 , respectively ) . CLINICAL IMPLICATION S Formal sex education and Kegel exercises were used as two non-pharmacologic approaches to improve the sexual function of women after menopause . STRENGTHS AND LIMITATIONS The main strength of this study was its design : a well-organized r and omized trial using precise eligibility criteria with a small sample loss . The second strength was the methods of intervention used , namely non-pharmacologic approaches that are simple , easily accessible , and fairly inexpensive . The main limitation of the study was our inability to objective ly assess the participants ' commitment to exercise and the sexual function of their partners . CONCLUSION Sex education programs and Kegel exercises could cause improvements in some domains of sexual function-specifically arousal , orgasm , and satisfaction-in postmenopausal women . Nazarpour S , Simbar M , Tehrani FR , Majd HA . Effects of Sex Education and Kegel Exercises on the Sexual Function of Postmenopausal Women : A R and omized Clinical Trial . J Sex Med 2017;14:959 - 967 Objective This study aims to evaluate the treatment effects of physical exercise on menopausal symptoms in middle-aged female medical staff experiencing perimenopausal syndrome . Methods A total of 157 female medical staff aged 40 to 55 years and with a Kupperman index score of 15 points or higher were r and omized 1:1 into an intervention group ( n = 78 ) or a control group ( n = 79 ) . Women in the intervention group were asked to perform aerobic physical exercise ( walking with strides ) three times a week or more , whereas those in the control group continued as normal . Measurements were taken at baseline and on weeks 4 , 8 , and 12 , with total Kupperman index score , scores on individual elements of the scale , weight , and waist circumference recorded . In addition , fasting blood glucose , triglycerides , total cholesterol , high-density lipoprotein cholesterol , and low-density lipoprotein cholesterol were recorded at baseline and on week 12 . The effects of physical exercise therapy on perimenopausal syndrome were evaluated by comparing changes in these parameters between the control group and the intervention group . Results Fifty-four and 57 women completed all three follow-ups in the intervention and control groups , respectively . On week 12 , the mean ( SD ) change in total Kupperman index score ( −9.23 [ 6.23 ] ) from baseline to week 12 ; the mean ( SD ) changes in individual scores for paresthesia ( −1.08 [ 1.51 ] ) , insomnia ( −1.00 [ 1.46 ] ) , irritability ( −1.00 [ 1.34 ] ) , joint or muscle pain ( −0.75 [ 0.74 ] ) , fatigue ( −0.56 [ 0.75 ] ) , headache ( −0.54 [ 0.75 ] ) , formication ( −0.38 [ 0.66 ] ) , and sexual life ( −0.62 [ 1.71 ] ) ; and the mean ( SD ) changes in total cholesterol ( −0.76 [ 0.63 ] mmol/L ) and triglycerides ( −0.20 [ 0.50 ] mmol/L ) were significantly higher in the intervention group than in the control group ( P < 0.05 ) . In the intervention group , total Kupperman index score , weight , body mass index , waist circumference , triglycerides , and total cholesterol were significantly lower on week 12 compared with baseline ( P < 0.05 ) . Conclusions Physical exercise can substantially reduce menopausal symptoms and improve blood lipid status and body weight OBJECTIVE The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms . STUDY DESIGN We conducted a 12-week 3 × 2 r and omized , controlled , factorial design trial . Peri- and postmenopausal women , 40 - 62 years old , were assigned r and omly to yoga ( n = 107 ) , exercise ( n = 106 ) , or usual activity ( n = 142 ) and also assigned r and omly to a double-blind comparison of omega-3 ( n = 177 ) or placebo ( n = 178 ) capsules . We performed the following interventions : ( 1 ) weekly 90-minute yoga classes with daily at-home practice , ( 2 ) individualized facility-based aerobic exercise training 3 times/week , and ( 3 ) 0.615 g omega-3 supplement , 3 times/day . The outcomes were assessed with the following scores : Menopausal Quality of Life Question naire ( MENQOL ) total and domain ( vasomotor symptoms , psychosocial , physical and sexual ) . RESULTS Among 355 r and omly assigned women who average age was 54.7 years , 338 women ( 95 % ) completed 12-week assessment s. Mean baseline vasomotor symptoms frequency was 7.6/day , and the mean baseline total MENQOL score was 3.8 ( range , 1 - 8 from better to worse ) with no between-group differences . For yoga compared to usual activity , baseline to 12-week improvements were seen for MENQOL total -0.3 ( 95 % confidence interval , -0.6 to 0 ; P = .02 ) , vasomotor symptom domain ( P = .02 ) , and sexuality domain ( P = .03 ) scores . For women who underwent exercise and omega-3 therapy compared with control subjects , improvements in baseline to 12-week total MENQOL scores were not observed . Exercise showed benefit in the MENQOL physical domain score at 12 weeks ( P = .02 ) . CONCLUSION All women become menopausal , and many of them seek medical advice on ways to improve quality of life ; little evidence -based information exists . We found that , among healthy sedentary menopausal women , yoga appears to improve menopausal quality of life ; the clinical significance of our finding is uncertain because of the modest effect ABSTRACT The aim of the authors in this r and omized controlled study was to assess the effect of exercise and nutrition education on quality of life and early menopausal symptoms . This trial was conducted in east Azerbaijan Province , Iran , during the period from 2013 to 2014 with 108 women allocated into one of four groups ( n = 27 in each group ) by block r and omization . The interventions received by the three intervention groups were : nutrition education , aerobic exercise , or exercise plus nutrition education . The control group did not receive any intervention . The Greene and MENQOL menopause symptom scales were completed before and at 8 and 12 weeks after the intervention . The mean Greene score was significantly lower than the control group in the exercise ( adjusted mean difference : −5.1 ) and exercise plus nutrition groups ( −8.0 ) at the end of week 8 and in the nutrition ( −4.8 ) , exercise ( −8.7 ) , and exercise plus nutrition ( −13.2 ) groups at the end of week 12 . Also , the mean MENQOL score was significantly lower than the control group in the exercise ( −8.3 ) and exercise plus nutrition groups ( −13.8 ) at the end of week 8 and in the nutrition ( −6.6 ) , exercise ( −13.5 ) , and exercise plus nutrition ( −22.1 ) groups at the end of week 12 . Nutrition education with aerobic exercise can improve quality of life INTRODUCTION Physical exercise including pelvic floor muscle ( PFM ) training seems to improve the sexual function of women with urinary incontinence . This effect in postmenopausal women who are continent has not yet been determined . AIM The aim of this study was to assess the effect of a 3-month physical exercise protocol ( PEP ) on the sexual function and mood of postmenopausal women . METHODS Thirty-two sedentary , continent , sexually active women who had undergone menopause no more than 5 years earlier and who had follicle stimulating hormone levels of at least 40 mIU/mL were enrolled into this longitudinal study . All women had the ability to contract their PFMs , as assessed by vaginal bimanual palpation . Muscle strength was grade d according to the Oxford Modified Grading Scale ( OMGS ) . A PEP was performed under the guidance of a physiotherapist ( M.M.F. ) twice weekly for 3 months and at home three times per week . All women completed the Sexual Quotient-Female Version ( SQ-F ) and the Hospital Anxiety and Depression Scale ( HADS ) before and after the PEP . MAIN OUTCOME MEASURES SQ-F to assess sexual function , HASDS to assess mood , and OMGS to grade pelvic floor muscle strength . RESULTS Thirty-two women ( 24 married women , eight women in consensual unions ) completed the PEP . Following the PEP , there was a significant increase in OMGS score ( 2.59 ± 1.24 vs. 3.40 ± 1.32 , P < 0.0001 ) and a significant decrease in the number of women suffering from anxiety ( P < 0.01 ) , but there was no effect on sexual function . CONCLUSION Implementation of our PEP seemed to reduce anxiety and improve pelvic floor muscular strength in sedentary and continent postmenopausal women . However , our PEP did not improve sexual function . Uncontrolled variables , such as participation in a long-term relationship and menopause status , may have affected our results . We suggest that a r and omized controlled trial be performed to confirm our results OBJECTIVE : Data on the sexual activity of middle-aged and older women are scant and vary widely . This analysis estimates the prevalence and predictors of sexual activity and function in a diverse group of women aged 40–69 years . METHODS : The Reproductive Risk Factors for Incontinence Study at Kaiser ( RRISK ) was a population -based study of 2,109 women aged 40–69 years who were r and omly selected from long-term Kaiser Permanente members . Women completed self-report question naires on sexual activity , comorbidities , and general quality of life . Logistic and linear regression and proportional odds models were used when appropriate to identify correlates of sexual activity , frequency , satisfaction , and dysfunction . RESULTS : Mean age was 55.9 ( ± 8) years and nearly three fourths of the women were sexually active . Of the sexually active women , 60 % had sexual activity at least monthly , approximately two thirds were at least somewhat satisfied , and 33 % reported a problem in one or more domains . Monthly or more frequent sexual activity was associated with younger age , higher income , being in a significant relationship , a history of moderate alcohol use , and lower body mass index ( BMI ) ( all P < .05 ) . Satisfaction with sexual activity was associated with African-American race , lower BMI , and higher mental health score ( all P < .05 ) . More sexual dysfunction was associated with having a college degree or greater , poor health , being in a significant relationship , and a low mental health score ( all P < .05 ) . CONCLUSION : Middle-aged and older women engage in satisfying sexual activity , and one third reported problems with sexual function . Demographic factors as well as some issues associated with aging can adversely affect sexual frequency , satisfaction , and function . LEVEL OF EVIDENCE : INTRODUCTION Pelvic floor muscle exercise ( PFME ) is recommended as a first-line treatment for urinary incontinence . However , a review of the literature suggests the effect of PFME on sexual function ( SF ) , particularly during pregnancy and the postpartum period , is understudied . AIM To assess the effect of PFME on SF during pregnancy and the postpartum period . METHODS The following data bases were search ed : CINAHL ( EBSCOhost ) , Health Collection ( Informit ) , PubMed ( National Center for Biotechnology Information ) , Embase ( Ovid ) , MEDLINE , Cochrane , Health Source , Scopus , Wiley , Health & Medical Complete ( ProQuest ) , Joanna Briggs Institute , and Google Scholar . Results from published r and omized controlled trials ( RCTs ) and non- RCTs from 2004 to January 2018 on pregnant and postnatal women were included . PEDro and Critical Appraisal Skills Programme scores were used to assess the quality of studies . Data were analysed using a qualitative approach . MAIN OUTCOME MEASURE The primary outcome was the impact of antenatal or postnatal PFME on at least 1 SF variable , including desire , arousal , orgasm , pain , lubrication , and satisfaction . The secondary outcome was the impact of PFME on PFM strength . RESULTS We identified 10 studies with a total of 3607 participants . These included 4 RCTs , 1 quasi-experimental study , 3 interventional cohort studies , and 2 long-term follow up cohort studies . No studies examined the effect of PFME on SF during pregnancy . 7 studies reported that PFME alone improved sexual desire , arousal , orgasm , and satisfaction in the postpartum period . CONCLUSION The current data needs to be interpreted in the context of the studies ' risk of bias , small sample sizes , and varying outcome assessment tools . The majority of the included studies reported that postnatal PFME was effective in improving SF . However , there is a lack of studies describing the effect of PFME on SF during pregnancy , and only minimal data are available on the postpartum period . More RCTs are needed in this area . Sobhgol SS , Priddis H , Smith CA , et al. The Effect of Pelvic Floor Muscle Exercise on Female Sexual Function During Pregnancy and Postpartum : A Systematic Review . Sex Med Rev 2019;7:13 - 28 BACKGROUND Polycystic ovary syndrome ( PCOS ) is a common condition characterized by hyper and rogenism , anthropometric changes ( increased weight and waist-to-hip ratio [ WHR ] ) , behavioral changes ( sexual dysfunction , anxiety , and depression ) , and reduced quality of life . Physical exercise may reduce many of the adverse effects of PCOS . However , no studies have yet evaluated the effects of aerobic exercise on the sexual function of women with PCOS . AIM To compare the effects of continuous and intermittent aerobic physical training on the sexual function and mood of women with PCOS . METHODS This is a secondary analysis of a controlled clinical trial in which women with PCOS ( 18 - 39 years of age ) were r and omly allocated to 1 of 3 groups for 16 weeks : continuous aerobic training ( CAT , n = 23 ) , intermittent aerobic training ( IAT , n = 22 ) , or no training ( control group , n = 24 ) . The Female Sexual Function Index ( FSFI ) was used to assess sexual function , and the Hospital Anxiety and Depression Scale ( HADS ) was used to assess anxiety and depression . MAIN OUTCOME MEASURE The main outcome measure used was the FSFI . OUTCOMES The primary outcomes were changes from baseline in total FSFI score and HAD scores at week 16 to prove the superiority of intermittent aerobic exercise compared with continuous aerobic exercise . RESULTS After 16 weeks , the CAT group had a significant increase in the total FSFI score , improvements in the FSFI domains of satisfaction and pain , and a reduction in the WHR . The CAT and IAT groups also had significantly lower levels of testosterone after 16 weeks . The IAT group had a significant increase in the total FSFI score and improvements in the desire , excitation , lubrication , orgasm , and satisfaction FSFI domains . The CAT and IAT groups both had significant reductions in anxiety and depression scores after 16 weeks . CLINICAL IMPLICATION S Aerobic physical training protocol s could be indicated to promote mental and sexual health in women with PCOS . STRENGTH & LIMITATIONS This is one of the first studies to examine the effects of different physical training protocol s on the sexual function of women with PCOS . The limitations of this study are that we did not consider diet or the frequency of sexual relations of participants with their partners . These factors could have interfered with the outcomes . CONCLUSION The CAT and IAT protocol s improved the sexual function and reduced the anxiety and depression of women with PCOS . Both protocol s were similar to improve FSFI domain scores . Lopes IP , Ribeiro VB , Reis RM , et al. Comparison of the Effect of Intermittent and Continuous Aerobic Physical Training on Sexual Function of Women With Polycystic Ovary Syndrome : R and omized Controlled Trial . J Sex Med 2018;15:1609 - 1619 Abstract Dyspareunia negatively affects women´s quality of life , and is a frequent complaint during the peri- and postmenopausal period . A r and omized trial evaluated sexual function , quality of life , pain , and pelvic floor muscle function of climacteric women aged between 40 and 60 years old who were sexually active and had complaints of dyspareunia for at least six months . They were assessed before and after their r and omization in one of the following interventions : the first group ( n = 21 ) received five one-hour sessions of thermotherapy for relaxation of pelvic floor muscles , myofascial release , and pelvic training ( pelvic floor muscle training — PFMT group ) . The second group ( n = 21 ) received five one-hour sessions during which heat was applied to the lower back with myofascial release of abdominal diaphragm , piriformis , and iliopsoas muscles , with no involvement of pelvic training ( lower back — LB group ) . Forty-two climacteric women with dyspareunia ( mean ± SD , PFMT group : 51.9 ± 5.3 years , LB group : 50.6 ± 4.7 years , Student ’s t-test , p = 0.397 ) were studied . Pain scores ( mean ± SEM ) in the PFMT group decreased from 7.77 ± 0.38 to 2.25 ± 0.30 ; and in the LB group from 7.62 ± 0.29 to 5.58 ± 0.49 ( generalized estimating equation — GEE model , p ≤ 0.001 for group , time , and interaction pairwise comparisons ) . Conclusion : The proposed pelvic floor muscle training protocol was effective to improve pain , quality of life , sexual function , and pelvic floor muscle function in climacteric women with dyspareunia OBJECTIVES To analyze the effects that a Pilates-based exercise program has on sleep quality , anxiety , depression and fatigue in community-dwelling Spanish postmenopausal women aged 60 and over . STUDY DESIGN A total of 110 women ( 69.15 ± 8.94 years ) participated in this r and omized controlled trial . They were r and omly allocated to either a control ( n = 55 ) or a Pilates ( n = 55 ) group . MAIN OUTCOME MEASURES Sleep quality and self-perceived fatigue were assessed by the Pittsburgh Sleep Quality Index ( PSQI ) and the Fatigue Severity Scale , respectively . Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale ( HADS ) . RESULTS Significant improvements were observed after Pilates training in all PSQI domains as well as in the PSQI total score , with small to medium-size effects , while significant between-group differences in post-intervention measures were observed only for sleep duration ( d = 0.69 ) and sleep disturbances ( d = 0.78 ) . Moreover , intra- and inter-group statistical differences were observed for depression ( d = 0.39 and d = 0.86 , respectively ) and for anxiety ( d = 0.43 and d = 1.27 respectively ) . Finally , participants in the Pilates group experienced a decrease in self-perceived fatigue after the intervention period ( d = 0.32 ) . CONCLUSIONS For community-dwelling Spanish postmenopausal women aged 60 years and over , a twelve-week Pilates exercise intervention has beneficial effects on sleep quality , anxiety , depression and fatigue OBJECTIVES Treatments for genitourinary syndrome of menopause ( GSM ) may not be suitable for all women , may not be completely effective , and may cause adverse effects . Therefore , there is a need to explore new treatment approaches . The objectives were to evaluate the feasibility of using a pelvic floor muscle training ( PFMT ) program in postmenopausal women with GSM , and to investigate its effect on symptoms , signs , activities of daily living ( ADL ) , quality of life ( QoL ) and sexual function . STUDY DESIGN Postmenopausal women with GSM participated in a single-arm feasibility study embedded in a r and omized controlled trial ( RCT ) on PFMT for urinary incontinence . This sub study was composed of two pre-intervention evaluations , a 12-week PFMT program and a post-intervention evaluation . MAIN OUTCOME MEASURES Feasibility was defined as study completion and participation in physiotherapy sessions and in-home exercises . The effects of the PFMT program were assessed by measuring GSM symptoms ( ' Most Bothersome Symptom ' approach , ICIQ-UI SF ) , GSM signs ( Vaginal Health assessment scale ) , GSM 's impact on ADL ( Atrophy Symptom question naire ) , QoL and sexual function ( ICIQ-VS , ICIQ-FLUTSsex ) and leakage episodes . RESULTS Thirty-two women participated . The study completion rate was high ( 91 % ) , as was participation in treatment sessions ( 96 % ) and in-home exercises ( 95 % ) . Post-intervention , there were significant reductions in GSM symptoms and signs ( p < 0.01 ) as well as in its impacts on ADL , QoL and sexual function ( p < 0.05 ) . CONCLUSIONS A study including a PFMT program is feasible , and the outcomes indicate PFMT to be an effective treatment approach for postmenopausal women with GSM and urinary incontinence . This intervention should be assessed through a RCT Objective : The life expectancy of women increases with the advancement in modern medicine , leading them to spent about two decades in menopausal state along with its associated complications . The process of aging triggers a deleterious cascade of physiological changes in the body . Hence , the aim of our study is to determine the effects of both aerobic and anaerobic exercises on estrogen level in postmenopausal osteoporotic females . Methodology : A r and omized control trial was conducted among 94 postmenopausal osteoporotic females , r and omly divided into two equal groups . The participants in Group A were assigned to perform aerobic exercise , whereas Group B performed resistance exercises . Each group performed exercises for 12 weeks , whereas reading was collected for blood estrogen level , fat mass , and muscle mass before exercise training and after 12 weeks of training . Results : Twelve weeks of aerobic and anaerobic exercise program based on the American College of Sports Medicine ( ACSM ) ; frequency , intensity , time , and type protocol has beneficial effect on estradiol level and lean mass , whereas inversely correlated with fat mass of postmenopausal osteoporotic female . Conclusion : The study concluded that 12 weeks of exercise programs was found to be effective in improving estradiol level of postmenopausal osteoporotic female . The efficacy of anaerobic exercise was found to be more potent on estradiol level and lean mass than aerobic exercises as only 36 sessions of resisted exercises performed during a period of 12 weeks provided more significant result than 72 session of aerobic exercises Background The adverse effects of menopause on sexual function could be mitigated by pelvic floor muscle ( PFM ) training . This study aim ed to investigate the effects of PFM exercises on sexual function in postmenopausal women . METHODS A r and omised clinical trial was conducted among 97 Iranian postmenopausal women , aged 40 to 60 years . The participants ' baseline sexual functions were assessed using the Female Sexual Function Index ( FSFI ) question naire . They were then r and omly design ated to two groups : ( 1 ) the intervention group , which received specific instructions on PFM exercises and was followed up on a weekly basis ; and ( 2 ) the control group , which received general information on menopause . After 12 weeks , the sexual functions of the participants were reassessed . RESULTS No significant difference was initially observed between the two groups in terms of demographic and socioeconomic characteristics and total scores of FSFI . After the intervention , however , the scores of arousal , orgasm and satisfaction were significantly higher in the intervention group ( 3.10 , 4.36 , and 4.84 vs 2.75 , 3.89 , and 4.36 respectively ; P<0.05 ) . CONCLUSION PFM exercises have the potential to improve the sexual function of postmenopausal women and are thus suggested to be included in healthcare packages design ed for postmenopausal women |
408 | 28,760,149 | Explicit attention for goal setting or priority setting by a professional was a common element in these multifactorial interventions .
Conclusions Collaborative goal setting and /or priority setting can probably best be integrated in complex care interventions . | Background It is challenging to use shared decision-making with patients who have a chronic health condition or , especially , multimorbidity .
A patient- goal -oriented approach can thus be beneficial .
This study aims to identify and evaluate studies on the effects of interventions that support collaborative goal setting or health priority setting compared to usual care for elderly people with a chronic health condition or multimorbidity . | OBJECTIVE To examine to what extent general practitioners in consultations after a geriatric assessment set shared health priorities with older patients experiencing multimorbidity and to what extent this was facilitated through patient-centered behavior . METHODS Observation of consultations embedded in a cluster r and omized controlled trial,(1 ) in which 317 patients from 41 general practice s received the STEP assessment followed by a care planning consultation with their GPs . GPs in the intervention group used a structured procedure for setting health ( care ) priorities in contrast to control GPs . A sample of 43 consultations ( 24 intervention ; 19 control ) were recorded , transcribed and analyzed with regard to priority setting and patient-centeredness . RESULTS Patient-centeredness was only moderately apparent in consultations dealing with complex care plans for older patients with multimorbidity . The shared determination of health priorities seemed unusual for both doctors and patients and was rarely practice d , albeit more frequently in intervention consultations . CONCLUSION Setting health care priorities with patients experiencing multimorbidity is ethically desirable and medically appropriate . Yet a short structured guide for doctors can not easily achieve this . PRACTICE IMPLICATION S More research is needed in regard to h and ling complex health needs of older patients . It requires a professional approach and training in patient-centered holistic care planning BACKGROUND General Practitioners ( GPs ) often have to simultaneously tackle multiple health problems of older patients . A patient-centred process that engages the patient in setting health priorities for treatment is needed . We investigated whether a structured priority- setting consultation reconciles the often-differing doctor-patient views on the importance of problems . DESIGN Cluster r and omised controlled trial with 40 GPs and their 317 consecutively recruited older patients . PROCEDURE Following a geriatric assessment , patients and doctors independently rated the importance of each uncovered problem . GPs then selected priorities with their patients in a consultation . Trained intervention GPs held a structured consultation and utilised the list of uncovered patient problems with their importance ratings to agree priorities . Untrained control GPs only used the patient 's problem list without importance ratings . MAIN OUTCOME Doctor-patient agreement on independent importance ratings two weeks after the priority- setting consultation . ANALYSIS Weighted kappa ( κw ) and multilevel logistic regression model . RESULTS Intervention GPs and their patients determined mutual priorities for 20 % of individual problems . In this process , GPs often succeeded in convincing their patients of the importance of vaccinations , lifestyle and cognitive issues . Likewise , patients convinced their GPs to prioritise their social and functional problems . Further treatment plans ensued in 84 % of these priority areas . The regression model adjusting for clusters and baseline characteristics did not demonstrate significant differences in doctor-patient agreement on problems between groups a two weeks later . CONCLUSION Differing views on the importance of health problems between GPs and older patients were not sustainably reconciled . The special consultation facilitated identification of priority problems for treatment despite differences in perceived importance of problems between patients and GPs . German clinical trials register drks 00000792 Background : older people often experience complex problems . Because of multiple problems , care for older people in general practice needs to shift from a ‘ problem-based , disease-oriented ’ care aim ing at improvement of outcomes per disease to a ‘ goal -oriented care ’ , aim ing at improvement of functioning and personal quality of life , integrating all healthcare providers . Feasibility and cost-effectiveness of this proactive and integrated way of working are not yet established . Design : cluster r and omised trial . Participants : all persons aged ≥75 in 59 general practice s ( 30 intervention , 29 control ) , with a combination of problems , as identified with a structured postal question naire with 21 questions on four health domains . Intervention : for participants with problems on ≥3 domains , general practitioners ( GPs ) made an integrated care plan using a functional geriatric approach . Control practice s : care as usual . Outcome measures : ( i ) quality of life ( QoL ) , ( ii ) activities of daily living , ( iii ) satisfaction with delivered health care and ( iv ) cost-effectiveness of the intervention at 1-year follow-up . Trial registration : Netherl and s trial register , NTR1946 . Results : of the 11,476 registered eligible older persons , 7,285 ( 63 % ) participated in the screening . One thous and nine hundred and twenty-one ( 26 % ) had problems on ≥3 health domains . For 225 r and omly chosen persons , a care plan was made . No beneficial effects were found on QoL , patients ' functioning or healthcare use/costs . GPs experienced better overview of the care and stability , e.g. less unexpected dem and s , in the care . Conclusions : GPs prefer proactive integrated care . ‘ Horizontal ’ care using care plans for older people with complex problems can be a valuable tool in general practice . However , no direct beneficial effect was found for older persons Objective To test the effectiveness of an integrated collaborative care model for people with depression and long term physical conditions . Design Cluster r and omised controlled trial . Setting 36 general practice s in the north west of Engl and . Participants 387 patients with a record of diabetes or heart disease , or both , who had depressive symptoms ( ≥10 on patient health question aire-9 ( PHQ-9 ) ) for at least two weeks . Mean age was 58.5 ( SD 11.7 ) . Participants reported a mean of 6.2 ( SD 3.0 ) long term conditions other than diabetes or heart disease ; 240 ( 62 % ) were men ; 360 ( 90 % ) completed the trial . Interventions Collaborative care included patient preference for behavioural activation , cognitive restructuring , grade d exposure , and /or lifestyle advice , management of drug treatment , and prevention of relapse . Up to eight sessions of psychological treatment were delivered by specially trained psychological wellbeing practitioners employed by Improving Access to Psychological Therapy services in the English National Health Service ; integration of care was enhanced by two treatment sessions delivered jointly with the practice nurse . Usual care was st and ard clinical practice provided by general practitioners and practice nurses . Main outcome measures The primary outcome was reduction in symptoms of depression on the self reported symptom checklist-13 depression scale ( SCL-D13 ) at four months after baseline assessment . Secondary outcomes included anxiety symptoms ( generalised anxiety disorder 7 ) , self management ( health education impact question naire ) , disability ( Sheehan disability scale ) , and global quality of life ( WHOQOL-BREF ) . Results 19 general practice s were r and omised to collaborative care and 20 to usual care ; three practice s withdrew from the trial before patients were recruited . 191 patients were recruited from practice s allocated to collaborative care , and 196 from practice s allocated to usual care . After adjustment for baseline depression score , mean depressive scores were 0.23 SCL-D13 points lower ( 95 % confidence interval −0.41 to −0.05 ) in the collaborative care arm , equal to an adjusted st and ardised effect size of 0.30 . Patients in the intervention arm also reported being better self managers , rated their care as more patient centred , and were more satisfied with their care . There were no significant differences between groups in quality of life , disease specific quality of life , self efficacy , disability , and social support . Conclusions Collaborative care that incorporates brief low intensity psychological therapy delivered in partnership with practice nurses in primary care can reduce depression and improve self management of chronic disease in people with mental and physical multimorbidity . The size of the treatment effects were modest and were less than the prespecified effect but were achieved in a trial run in routine setting s with a deprived population with high levels of mental and physical multimorbidity . Trial registration IS RCT N80309252 PURPOSE Guided Care ( GC ) is a model of health care for multimorbid older adults that is provided by a registered nurse who works with the patients ' primary care physician ( PCP ) . The purpose of this study was to determine whether GC improves patients ' primary caregivers ' depressive symptoms , strain , productivity , and perceptions of the quality of care recipients ' chronic illness care . DESIGN AND METHODS A cluster-r and omized controlled trial of GC was conducted within 14 PCP teams . The study sample included 196 primary caregivers who completed baseline and 18-month surveys and whose care recipients remained alive and enrolled in the GC study for 18 months . Caregiver outcomes included the following : depressive symptoms ( Center for Epidemiological Studies -Depression scale ) , strain ( Modified Caregiver Strain Index ) , the quality of care recipients ' chronic illness care [ Patient Assessment of Chronic Illness Care ( PACIC ) ] , and personal productivity ( Work Productivity and Activity Impairment question naire , adapted for caregiving ) . RESULTS In multivariate regression models , between-group differences in depression , strain , work productivity , and regular activity productivity were not statistically significant after 18 months , but GC caregivers reported the overall quality of their recipients ' chronic illness care to be significantly higher ( adjusted beta = 0.40 , 95 % confidence interval : 0.14 - 0.67 ) . Quality was significantly higher in 4 of 5 PACIC subscales , reflecting the dimensions of goal setting , coordination of care , decision support , and patient activation . IMPLICATION S GC improved the quality of chronic illness care received by multimorbid care recipients but did not improve caregivers ' depressive symptoms , affect , or productivity BACKGROUND The quality of health care for older Americans with chronic conditions is suboptimal . OBJECTIVE To evaluate the effects of “ Guided Care ” on patient-reported quality of chronic illness care . DESIGN Cluster-r and omized controlled trial of Guided Care in 14 primary care teams . PARTICIPANTS Older patients of these teams were eligible to participate if , based on analysis of their recent insurance cl aims , they were at risk for incurring high health-care costs during the coming year . Small teams of physicians and their at-risk older patients were r and omized to receive either Guided Care ( GC ) or usual care (UC).INTERVENTION“Guided Care ” is design ed to enhance the quality of health care by integrating a registered nurse , trained in chronic care , into a primary care practice to work with 2–5 physicians in providing comprehensive chronic care to 50–60 multi-morbid older patients . MEASUREMENTS Eighteen months after baseline , interviewers blinded to group assignment administered the Patient Assessment of Chronic Illness Care ( PACIC ) survey by telephone . Logistic and linear regression was used to evaluate the effect of the intervention on patient-reported quality of chronic illness care . RESULTS Of the 13,534 older patients screened , 2,391 ( 17.7 % ) were eligible to participate in the study , of which 904 ( 37.8 % ) gave informed consent and were cluster-r and omized . After 18 months , 95.3 % and 92.2 % of the GC and UC recipients who remained alive and eligible completed interviews . Compared to UC recipients , GC recipients had twice greater odds of rating their chronic care highly ( aOR = 2.13 , 95 % CI = 1.30–3.50 , p = 0.003 ) . CONCLUSION Guided Care improves self-reported quality of chronic health care for multi-morbid older persons BACKGROUND The quality of health care for older Americans with multiple chronic conditions is suboptimal . We design ed " Guided Care " ( GC ) to enhance quality of care by integrating a registered nurse , intensively trained in chronic care , into primary care practice s to work with physicians in providing comprehensive chronic care to 50 - 60 multimorbid older patients . METHODS We hypothesized that GC would improve the quality of health care for this population . In 2006 , we began a cluster-r and omized controlled trial of GC at eight practice s ( n = 49 physicians ) . Older patients of these practice s were eligible to participate if they were at risk for using health services heavily during the coming year . Teams of two to five physicians and their at-risk older patients were r and omized to either GC or usual care ( UC ) . Six months after baseline , participants rated the quality of their health care by answering vali date d closed-ended questions from telephone interviewers who were masked to group assignment . RESULTS Of the 13,534 older patients screened , 2391 ( 17.7 % ) were eligible to participate in the study , of which 904 ( 37.8 % ) gave informed consent and were cluster-r and omized . After 6 months , 93.8 % and 93.2 % of the GC and UC participants who remained alive and eligible completed telephone interviews . GC participants were more likely than UC participants to rate their care highly ( adjusted odds ratio = 2.0 , 95 % confidence interval , 1.2 - 3.4 , p = .006 ) , and primary care physicians were more likely to be satisfied with their interactions with chronically ill older patients and their families ( p < .05 ) . CONCLUSIONS GC improves important aspects of the quality of health care for multimorbid older persons . Additional data will become available as this trial continues |
409 | 29,417,326 | Stents combination therapy was also associated with a more favorable overall survival .
The risks of stent migration , aspiration pneumonia , and restenosis were lower in the stents combination group compared to stents alone , while the risks of severe pain , hemorrhage , and fistula formation were higher .
Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison .
The risk of fistula formation and hemorrhage were higher in the stents-alone group , while the risk of perforation was lower , compared to brachytherapy alone .
Quality of life improvements were seen in all treatment groups , but were not pooled in analysis due to differing methods of measurement .
Discussion While there appears to be no immediate short-term differences , those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone .
The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores . | Introduction More than 50 % of patients with esophageal cancer already have inoperable disease at the time of diagnosis .
Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality .
We set out to perform a systematic review and meta- analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement , survival , and adverse events . | PURPOSE To investigate whether a combination of self-exp and ing metal stent ( SEMS ) and brachytherapy provided more rapid and prolonged effect on dysphagia without increased pain compared to brachytherapy alone in patients with incurable oesophageal cancer . METHODS 41 Patients were r and omised to SEMS followed by brachytherapy , 8 Gy × 3 ( n=21 ) or brachytherapy alone , 8 Gy × 3 ( n=20 ) . Change in dysphagia and pain three and seven weeks after r and omisation ( FU1 and FU2 ) was assessed by patient-reported outcome . Dysphagia , other symptoms and health-related quality of life were assessed every four weeks thereafter . The study was closed before the estimated patient-number was reached due to slow recruitment . RESULTS Patients receiving SEMS followed by brachytherapy had significantly improved dysphagia at FU1 compared to patients receiving brachytherapy alone ( n=35 ) . Difference in pain was not observed . At FU2 , patients in both arms ( n=21 ) had less dysphagia . Four patients in the combined treatment arm experienced manageable complications , no complications occurred after brachytherapy alone . CONCLUSION For the relief of dysphagia , SEMS followed by brachytherapy is preferable and safe for patients in need of immediate alleviation , while brachytherapy with or without preceding SEMS provides relief within a few weeks after treatment PURPOSE To prospect ively compare the response to treatment with a self-exp and able esophageal stent loaded with iodine 125 ( (125)I ) seeds for intraluminal brachytherapy versus the response to treatment with a conventional self-exp and able covered stent in patients with advanced esophageal cancer . MATERIAL S AND METHODS The study protocol was approved by the institutional ethics committee , and informed consent was obtained from each patient . Patients from one institution who had dysphagia caused by inoperable esophageal cancer were r and omly assigned to receive treatment with a stent loaded with (125)I seeds ( irradiation stent group ) or a conventional covered stent ( control group ) . After stent implantation , the outcomes were measured in terms of relief of dysphagia , survival time , and complications related to the procedure . Dysphagia was assigned a grade . A P value of less than .05 was considered to indicate a significant difference . RESULTS The stent was successfully placed in the diseased esophagus in all 53 patients ( 27 patients in the irradiation stent group and 26 patients in the control group ) . The dysphagia grade s significantly improved in both groups within the 1st month after stent placement but were better in the irradiation stent group than in the control group after 2 months ( P < .05 ) . The median and mean survival times were better in the irradiation stent group than in the control group , and the differences were significant ( P < .001 ) . Hemorrhage occurred in 16 ( 30 % ) patients in both groups combined during follow-up . CONCLUSION In patients with advanced esophageal cancer , treatment with an esophageal stent loaded with (125)I seeds , compared with that with a conventional covered stent , has potential benefit in that it allows a slightly longer relief of dysphagia and extended survival Objective To relieve dysphagia is the main goal in palliative treatment of patients with incurable cancer of the oesophagus or the gastro-oesophageal junction . The aim of this prospect i ve , r and omized multicentre study was to compare stent placement and brachytherapy regarding health economy and clinical outcomes . Methods Patients with incurable cancer of the oesophagus or gastro-oesophageal junction were r and omized to receive a self-exp and able metallic stent or 3 × 7 Gy brachytherapy . At clinical follow-up visits , dysphagia was scored and health care consumptions were recorded . Costs were based on hospital debits . Total lifetime healthcare consumption costs and costs for the initial treatments were calculated and a sensitivity analysis was conducted . Results Thirty patients were r and omized to each treatment group . There was no difference in survival or complication rates between the two treatment strategies . There was a significant difference in the change of dysphagia scores between the time of inclusion and the 1-month follow-up visit , in favour of the stented group ( P=0.03 ) . This difference had disappeared at 3 months . Median total lifetime costs were & U20AC;17 690 for the stented group compared with & U20AC;33 171 for the brachytherapy group ( P=0.005 ) . This difference was due to higher costs for the initial treatment ( & U20AC;4615 versus & U20AC;23 857 , P<0.0001 ) . Sensitivity analyses showed that the charges for a brachytherapy session had to be reduced from & U20AC;6092 to & U20AC;4222 ( 31 % ) to make this therapeutic concept cost-competitive . Conclusion Stenting is currently more cost-effective compared with fractionated 3 × 7 Gy brachytherapy for patients with incurable cancer of the oesophagus and gastro-oesophageal junction Metal stent placement and single dose brachytherapy are commonly used treatment modalities for the palliation of inoperable oesophageal carcinoma . We investigated generic and disease-specific health-related quality of life ( HRQoL ) after these palliative treatments . Patients with dysphagia from inoperable oesophageal carcinoma were r and omised to placement of a covered Ultraflex stent ( n = 108 ) or single dose ( 12 Gy ) brachytherapy ( n = 101 ) . We obtained longitudinal data on disease-specific ( dysphagia score , European Organisation for Research and Treatment of Cancer ( EORTC ) OES-23 , visual analogue pain scale ) and generic ( EORTC Quality of Life-Core 30 Question naire ( QLQ-C30 ) , Euroqol (EQ)-5D ) HRQoL at monthly home visits by a specially-trained research nurse . We compared HRQoL between the two treatments and analysed changes in HRQoL during follow-up . Dysphagia improved more rapidly after stent placement than after brachytherapy , but long-term relief of dysphagia was better after brachytherapy . For generic HRQoL , there was an overall significant difference in favour of brachytherapy on four out of five functional scales of the EORTC QLQ-C30 ( role , emotional , cognitive and social ) ( P < 0.05 ) . Generic HRQoL deteriorated over time on all functional scales of the EORTC QLQ C-30 and EQ-5D , in particular physical and role functioning ( on average -23 and -24 on a 100 points scale during 0.5 years of follow-up ) . This decline was more pronounced in the stent group . Major improvements were seen on the dysphagia and eating scales of the EORTC OES-23 , in contrast to other scales of this disease-specific measure , which remained almost stable during follow-up . Reported levels of chest or abdominal pain remained stable during follow-up in both treatment groups , general pain levels increased to a minor extent . The effects of single dose brachytherapy on HRQoL compared favourably to those of stent placement for the palliation of oesophageal cancer . Future studies on palliative care for oesophageal cancer should at least include generic HRQoL scales , since these were more responsive in measuring patients ' functioning and well-being during follow-up than disease-specific HRQoL scales OBJECTIVE To evaluate the benefits of post-stenting radiotherapy and /or chemotherapy for unresectable esophageal carcinoma . METHODS Fifty-three patients with unresectable esophageal carcinoma were r and omly divided into two groups : patients in group A ( n = 27 ) were treated with stenting alone , and those in group B ( n = 26 ) were treated with stenting followed by radiotherapy and /or chemotherapy . Comparison was made by assessing their survival time , quality of life ( QOL ) , degree of dysphagia , and stenting-related morbidity , respectively . RESULTS There was no statistically significant improvement in dysphagia and QOL between the two groups . Although there was no difference in the frequency of stenting-related complications , re-stenosis occurred much less frequently in group B patients ( P = 0.007 ) . The mean survival time of patients was 245 + /- 41 days and 262 + /- 43 days in group A and group B , respectively . There was no significant difference between the two groups ( P = 0.813 ) . CONCLUSION Besides decreased recurrence of stenosis , post-stenting radiotherapy and /or chemotherapy does not provide additional benefits for survival BACKGROUND Brachytherapy was found to be preferable to metal stent placement for the palliation of dysphagia because of inoperable esophageal cancer in the r and omized SIREC trial . The benefit of brachytherapy , however , only occurred after a relatively long survival . The objective is to develop a model that distinguishes patients with a poor prognosis from those with a relatively good prognosis . METHODS Survival was analyzed with Cox regression analysis . Dysphagia-adjusted survival ( alive with no or mild dysphagia ) was studied with Kaplan-Meier analysis . Patient data is from the multicenter , r and omized , controlled trial ( SIREC , n = 209 ) and a consecutive series ( n = 396 ) . Patients received a stent or single-dose brachytherapy . RESULTS Significant prognostic factors for survival included tumor length , World Health Organization performance score , and the presence of metastases ( multivariable p < 0.001 ) . A simple score , which also included age and gender , could satisfactorily separate patients with a poor , intermediate , and relatively good prognosis within the SIREC trial . For the poor prognosis group , the difference in dysphagia-adjusted survival was 23 days in favor of stent placement compared with brachytherapy ( 77 vs. 54 days , p = 0.16 ) . For the other prognostic groups , brachytherapy result ed in a better dysphagia-adjusted survival . CONCLUSIONS A simple prognostic score may help to identify patients with a poor prognosis in whom stent placement is at least equivalent to brachytherapy . If further vali date d , this score can provide an evidence -based tool for the selection of palliative treatment in esophageal cancer patients Background A majority of patients with esophageal cancer present with inoperable disease and require rapid and long-lasting palliation of dysphagia . Study aim To compare the duration of relief of dysphagia in patients with inoperable esophageal cancer treated with esophageal stenting alone or a combination of esophageal stenting and external beam radiotherapy ( EBRT ) , and to assess overall survival , treatment-related complications , and quality of life ( QOL ) in the two groups . Patients and methods Patients with inoperable esophageal cancer and with high grade dysphagia were r and omized to receive esophageal stenting with self-exp and able metal stent ( Ultraflex ) alone ( Group I ) , versus a combination of stenting followed by EBRT ( 30 gray in ten divided fractions over 2 weeks ) ( Group II ) . Dysphagia relief , overall survival , QOL ( using European Organisation for Research and Treatment of Cancer Quality of Life Question naire-C30 , version 3 ) , and treatment-related complications were assessed in the two groups . Results From April 2007 to March 2009 , 84 patients were r and omized to receive esophageal stent alone ( 42 patients ) or a combination of stent and EBRT ( 42 patients ) . The two groups were comparable in demographics , tumor characteristics , indications for palliative treatment , and pretreatment dysphagia score . Dysphagia scores improved significantly in both groups following stent insertion . However , dysphagia relief was more sustained in Group II than in Group I ( 7 vs. 3 months , p = 0.002 ) . Overall median survival was significantly higher in Group II than in Group I ( 180 vs. 120 days , p = 0.009 ) . Addition of radiotherapy following stenting prolonged the mean dysphagia-free survival ( 118.6 ± 55.8 vs. 96.8 ± 43.0 days , p = 0.054 ) . There was significant improvement in all QOL parameters at 1 week after stenting . The QOL , however , significantly declined immediately after radiotherapy . There was no treatment-related mortality , and the incidence of complications was similar in the two groups . Conclusion Post-stenting EBRT effectively prolongs duration of dysphagia relief and improves overall survival in inoperable esophageal cancer SUMMARY Esophageal cancer often presents as advanced stage disease with a dismal prognosis , with only 10 - 15 % of patients surviving 5 years . Therefore , in a large proportion of patients , palliative treatment is the only option available . The aim of this study was to prospect ively compare the palliative effect of self-exp and able stent placement with that of endoluminal brachytherapy regarding the effect on quality of life and on specific symptoms . Sixty-five patients with advanced cancer of the esophagus or gastroesophageal junction were r and omized to treatment with either an Ultraflex exp and able stent or high-dose-rate endoluminal brachytherapy with 7 Gy x 3 given in 2 - 4 weeks . Clinical assessment and health-related quality of life ( HRQL ) were measured at inclusion and 1 , 3 , 6 , 9 and 12 months later . The HRQL was measured with st and ardized question naires ( European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 , European Organization for Research and Treatment of Cancer Quality of Life Question naire Oesophageal Module and Hospital Anxiety and Depression Scale ) . Twenty-eight patients completed the stent treatment and 24 patients the brachytherapy . The group of patients treated with stent reported significantly better HRQL scores for dysphagia ( P < 0.05 ) at the 1-month follow-up , but most other HRQL scores , including functioning and symptom scales , deteriorated . Among brachytherapy-treated patients , improvement was found for the dysphagia-related scores at the 3-months follow-up , whereas other significant changes of scores were few . The median survival time was comparable in the two groups ( around 120 days ) . In conclusion , insertion of self-exp and able metal stents offered a more instant relief of dysphagia compared to endoluminal brachytherapy , but HRQL was more stable in the brachytherapy group BACKGROUND The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer . We aim ed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer . METHODS In this multicentre , single-blind , r and omised , phase 3 trial , we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China . We included adult patients ( aged ≥ 20 years ) with progressive dysphagia , unresectable tumours due to extensive lesions , metastases , or poor medical condition , and with clear consciousness , cooperation , and an Eastern Cooperative Oncology Group ( ECOG ) performance status score of 0 - 3 . Eligible patients were r and omly assigned ( in 1:1 ratio , no stratification ) to receive either a stent loaded with (125)iodine radioactive seeds ( irradiation group ) or a conventional oesophageal stent ( control group ) . The primary endpoint was overall survival . Survival analyses were done in a modified intention-to-treat group . This study is registered with Clinical Trials.gov , number NCT01054274 . FINDINGS Between Nov 1 , 2009 , and Oct 31 , 2012 , 160 patients were r and omly assigned to receive treatment with either an irradiation stent ( n=80 ) or a conventional stent ( n=80 ) . During a median follow-up of 138 days ( IQR 72 - 207 ) , 148 stents ( 73 in the irradiation group and 75 in the control group ) were successfully placed into the diseased oesophagus in 148 participants . Median overall survival was 177 days ( 95 % CI 153 - 201 ) in the irradiation group versus 147 days ( 124 - 170 ) in the control group ( p=0.0046 ) . Major complications and side-effects of the treatment were severe chest pain ( 17 [ 23 % ] of 73 patients in the irradiation group vs 15 [ 20 % ] of 75 patents in the control group ) , fistula formation ( six [ 8 % ] vs five [ 7 % ] ) , aspiration pneumonia ( 11 [ 15 % ] vs 14 [ 19 % ] ) , haemorrhage ( five [ 7 % ] vs five [ 7 % ] ) , and recurrent dysphagia ( 21 [ 28 % ] vs 20 [ 27 % ] ) . INTERPRETATION In patients with unresectable oesophageal cancer , the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-exp and able metallic stent Background Oesophageal cancer is often diagnosed at an advanced stage , with poor prognosis and severe morbidity . In majority of cases , palliative treatment is the only option available |
410 | 29,458,744 | This estimate 's differences were robust in alcohol consumption and sleep apnoea definitions , study design , and quality but was greater in Low and Middle Income Country locations .
Conclusion These findings suggest that alcohol consumption is associated with a higher risk of sleep apnoea , further supporting evidence that reducing alcohol intake is of potential therapeutic and preventive value in this condition | Objective A systematic review and meta- analysis of the association between alcohol consumption and risk of sleep apnoea in adults . | Objective . Determine the association between obstructive sleep apnea ( OSA ) and auditory dysfunction in older subjects . Study Design . Cross-sectional study . Setting . Hospital volunteer helpers undergoing question naire , morphometry measurement , auditory examinations , and polysomnography between 2008 and 2009 . Subjects and Methods . In total , 224 subjects older than 50 years were r and omly sample d for above evaluation and testing . The effects of OSA on the peripheral auditory function , represented by averaged pure-tone threshold of low frequencies ( PTA-low ) and high frequencies ( PTA-high ) , and central auditory function , shown by pitch pattern sequence ( PPS scores ) , were analyzed . Results . The mean ± SD age was 61.2 ± 6.7 years . OSA was confirmed in 6 of 98 women ( 6.1 % ) and 28 of 126 men ( 22.2 % ) . After adjusting for age , gender , and other variables , OSA did not show a significant positive association with PTA-low or PTA-high for all subjects . Conversely , there was a significant negative association between OSA and PPS scores for all subjects , even after adjusting for age , gender , and other variables . When OSA and central obesity together were taken into account in the multivariate linear regression analysis , OSA still showed significant association with PPS score for all subjects . Conclusion . OSA is independently associated with poorer central auditory function in older subjects Abstract Obstructive sleep apnea ( OSA ) is a common disorder , characterized by cyclic cessation of airflow for 10 seconds or more . There is growing awareness that OSA is related to the development and progression of cardiovascular disease . However , only a few studies have associated OSA directly to major cardiovascular events . The aim of this study was to evaluate the relationship between OSA and cardiovascular morbidity in a well defined population of patients .The electronic data base of the central district of a major health management organization was search ed for all patients diagnosed with OSA in 2002–2010 . For each patient identified , an age- and sex-matched patient was r and omly selected from the members of the same health management organization who did not have OSA . Data on demographics , socioeconomic status , and relevant medical parameters were collected as well . The study population included 2797 patients , average age 58.1 , in which 76.6 % were males . There was a significant correlation between OSA and the presence of ischemic heart disease ( P < 0.001 ) , pulmonary hypertension ( P < 0.001 ) , congestive heart failure ( P < 0.001 ) , cardiomyopathy ( P = 0.003 ) , and arrhythmia ( P < 0.001 ) . OSA was also significantly correlated with low socioeconomic status ( P < 0.001).OSA and cardiovascular disease were strongly correlated . As such , early diagnosis and treatment of OSA may change the course of both diseases . We suggest that sleep disordered breathing should be routinely assessed in patients with cardiovascular problems . An ear – nose – throat evaluation may also be important to rule out anatomic disorders that cause upper airway obstruction Background The Berlin Question naire ( BQ ) is a useful tool to identify the high-risk group for obstructive sleep apnea ( OSA ) in the primary care sites or hospital , but the usefulness of the BQ to identify the high-risk group for OSA in the general population has not been evaluated . The purpose of our study was to develop the Korean version of the BQ ( KBQ ) and evaluate the usefulness of the BQ in identifying patients with OSA in the general population . Methods A total of 1,305 subjects were included in a population -based door-to-door cross-sectional study . For validation of the KBQ , an overnight polysomnography ( PSG ) was performed on 101 subjects who were r and omly selected considering their age , sex , and risk group classification at a controlled sleep laboratory . Results The KBQ showed a relatively good to excellent internal consistency ( Cronbach ’s α correlation 0.64–0.78 ) and test – retest reliability ( intraclass correlation 0.92 ) . The apnea – hypopnea index ( AHI ) was significantly correlated with the scores in each category and the total scores of the KBQ . In addition , high risk grouping based on the KBQ predicted an AHI ≥ 5 with a sensitivity of 0.69 and a specificity of 0.83 . According to the risk categorization based on the KBQ , 26.1 % subjects were in the high-risk group for OSA which was similar to the prevalence of OSA in a previous large epidemiological study using PSG in Korea . Conclusion This is the first study to confirm the usefulness of the BQ as a screening tool for OSA by prioritizing subjects at high risk for OSA in the general population STUDY OBJECTIVES Experimental evidence indicates that alcohol use near bedtime may exacerbate sleep disordered breathing ( SDB ) . However , scarce research has examined the relation between moderate habitual alcohol use and objective ly assessed SDB , and it is unclear whether patients with SDB , or those at risk for SDB , should be counseled to avoid alcohol regardless of proximity to bedtime . In this population -based epidemiology study , our objective is to measure the association of SDB with usual alcohol consumption habits . METHODS Men ( N = 775 ) and women ( N = 645)--initially r and omly selected from a working population --participating in the Wisconsin Sleep Cohort Study were evaluated for alcohol consumption and SDB . The apnea-hypopnea index ( AHI , events/hour ) was determined by in-laboratory polysomnography . AHI > 5 defined " mild or worse " SDB and AHI > 15 defined " moderate or worse " SDB . Alcohol consumption ( drinks/day ) was assessed by question naire . Potential confounding or interacting variables such as smoking , body mass index , and medication use , were measured by clinical assessment and question naire . RESULTS Relative to men who consumed less alcohol , for each increment of one drink per day , men who consumed more alcohol had 25 % greater odds of mild or worse SDB ( OR = 1.25 , 95 % CI = 1.07 - 1.46 , p = 0.006 ) . Among women , minimal to moderate alcohol consumption was not significantly associated with increased risk of SDB . DISCUSSION In men , increased usual alcohol consumption was associated with increased risk of mild or worse SDB . Persons with SDB might benefit from generally reduced alcohol consumption and not just avoidance near bedtime OBJECTIVE Obstructive sleep apnea ( OSA ) has been recognized in the Western world as a public health burden , but there has been no community-based study performed to assess the prevalence of the condition in India . The study was performed to assess the prevalence and risk factors of OSA in a semi-urban Indian population . DESIGN A two-stage , cross-sectional , community-based prevalence study . SETTING A semi-urban community in Delhi . DURATION Two years ( 2003 to 2005 ) . PATIENTS AND PARTICIPANTS All citizens residing in the community who were 30 to 60 years of age . Exclusion criteria included those patients with recent myocardial infa rct ion , upper airway surgery , class III/IV congestive heart failure , pregnancy , hypothyroidism on treatment , acromegaly , chronic renal failure , systemic steroid treatment , and hormone replacement therapy . INTERVENTION An OSA assessment was performed in 2,400 subjects who were screened in stage 1 of the study by means of a sleep question naire . Subjects were then divided into habitual and nonhabitual snorers . Eighty-three r and omly selected habitual snorers and 80 nonhabitual snorers were invited to participate in stage 2 of the study , which consisted of in-hospital polysomnography studies . OBSERVATIONS AND RESULTS A total of 2,150 subjects returned question naires ( response rate , 90 % ) . Of 550 habitual snorers and 1,596 nonhabitual snorers , 77 habitual snorers and 73 nonhabitual snorers underwent polysomnography . A total of 36 habitual snorers ( 46.75 % ) and 2 nonhabitual snorers ( 2.73 % ) were found to have OSA , giving prevalence rates of 13.74 % and 3.57 % , respectively , for OSA and OSA syndrome ( OSAS ) on extrapolation . Multivariate analysis revealed that male gender , age , obesity ( defined by a high body mass index ) , and waist/hip ratio as significant risk factors for OSAS . CONCLUSIONS This study demonstrated that the risk factors and prevalence for OSA in India are similar to those in the West , which is contrary to the findings of some previous reports , which had a strong inclusion bias Nasal continuous positive airway pressure ( nasal CPAP ) and polysomnography were used to analyze the time course of the effect of bedtime ethanol on resistance of upper airways and on the number of respiratory pauses during sleep . On one night , six asymptomatic nonalcoholic male snorers drank 2 ml/kg of 100 proof vodka mixed in orange juice ( ethanol dose , 0.79 gm/kg , giving a peak blood alcohol level of 71.8 + /- 33.3 mg/dl ) . On a second night they received a placebo ( 1 - 2 drops of vodka floated on top of the orange juice ) . We measured ( a ) the minimum nasal ( CPAP ) required to eliminate snoring , ( b ) the number of hypopneas and apneas during each hour of sleep and ( c ) the arterial oxygen saturation ( SaO2 ) by ear oximetry . On the alcohol night there was a significant increase in the CPAP pressure required to eliminate snoring ( placebo 4.8 + /- 1.7 cm H2O , alcohol 6.2 + /- 1.5 cm H2O ) . The number of respiratory events per hour of sleep ( apnea index ) was 7.5 + /- 2.1 for ethanol nights versus 3.8 + /- 2.7 for placebo nights ( p less than 0.0125 ) . An apnea index of greater than 5 is generally considered abnormal . There was no significant difference in the number of desaturation events ( declines of 4 % or more in the SaO2 ) or in the mean SaO2 , but the minimum SaO2 was significantly lower on the ethanol night ( placebo 89.8 % + /- 1.6 , alcohol 86.8 % + /- 2.7 , p less than 0.05 ) . The effect of this dose of alcohol on airway resistance was most pronounced during the first 2 hr after ingestion BACKGROUND Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies . We performed a prospect i ve , population -based study of the association between objective ly measured sleep-disordered breathing and hypertension ( defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications ) . METHODS We analyzed data on sleep-disordered breathing , blood pressure , habitus , and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study ( and after eight years of follow-up in the case of 184 of these participants ) . Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing , as defined by the apnea-hypopnea index ( the number of episodes of apnea and hypopnea per hour of sleep ) . The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status , body-mass index , neck and waist circumference , age , sex , and weekly use of alcohol and cigarettes . RESULTS Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line , the odds ratios for the presence of hypertension at follow-up were 1.42 ( 95 percent confidence interval , 1.13 to 1.78 ) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none , 2.03 ( 95 percent confidence interval , 1.29 to 3.17 ) with an apnea-hypopnea index of 5.0 to 14.9 events per hour , and 2.89 ( 95 percent confidence interval , 1.46 to 5.64 ) with an apnea-hypopnea index of 15.0 or more events per hour . CONCLUSIONS We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors . The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population Apnea during sleep has been associated with both increased pharyngeal resistance and nasal obstruction . Alcohol can worsen obstructive sleep apnea , but its influence on pharyngeal resistance and nasal patency has not been evaluated . Accordingly , we determined the effects of alcohol on pharyngeal and nasal resistances in 11 normal awake subjects on 2 separate days . Baseline pharyngeal resistance prior to placebo and alcohol was not significantly different . After placebo , pharyngeal resistance did not change significantly . However , after alcohol , pharyngeal resistance increased from 1.9 + /- 0.5 ( SEM ) to 3.3 + /- 0.8 cm H2O/L/s at 45 min ( p less than 0.05 ) and returned to near baseline level by 90 min . Baseline nasal resistance varied considerably within subjects on the 2 days , but the mean values for baseline nasal resistance on alcohol and placebo days were not significantly different . Nasal resistance did not change after placebo , but after alcohol , nasal resistance increased from 2.4 + /- 0.9 at baseline to 3.7 + /- 0.8 at 45 min ( NS ) and to 4.3 + /- 1.2 cm H2O/L/s at 90 min ( p less than 0.05 ) . We conclude that a decrease in pharyngeal airway size and an increase in nasal resistance may account for alcohol 's ability to worsen obstructive sleep apnea The objectives of this study were to describe the prevalence of snoring , observed apneas , and daytime sleepiness in older men and women , and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases ( CVD ) . A cross-sectional design was employed to study sleep problems , CVD , general health , psychosocial factors , and medication use . The subjects were participants in the Cardiovascular Health Study , which included 5,201 adults , aged 65 and older , who were recruited from a r and om sample of Medicare enrollees in four U.S. communities . Study measures employed were sleep questions , echocardiography , carotid ultrasound , resting electrocardiogram , cognitive function , cardiopulmonary symptoms and diseases , depression , independent activities of daily living ( IADLs ) , and benzodiazepine use . Thirty-three percent of the men and 19 % of the women reported loud snoring , which was less frequent in those over age 75 . Snoring was positively associated with younger age , marital status , and alcohol use in men , and obesity , diabetes , and arthritis in women . Snoring was not associated , however , with cardiovascular risk factors or clinical CVD in men or women . Observed apneas were reported much less frequently ( 13 % of men and 4 % women ) than snoring , and they were associated with alcohol use , chronic bronchitis , and marital status in men . Observed apneas were associated with depression and diabetes in women . In both men and women , daytime sleepiness was associated with poor health , advanced age , and IADL limitations . The conclusions of the study were that loud snoring , observed apneas , and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons With many epidemiologic studies made to establish the prevalence of sleep-disordered breathing ( SDB ) and obstructive sleep apnea syndrome ( OSAS ) in Western countries , no such data have been reported in Korea . The purpose of this study was to examine the prevalence of SDB and OSAS , and their related factors in Korean adults aged 40 - 69 years . Among the total of 5,020 participants at the baseline examination of the Korean Health and Genome Study , a r and om sample of 457 men and women was studied with employment of overnight full polysomnography to determine the prevalence of SDB and OSAS . The prevalence of SDB ( apnea-hypopnea index > or = 5 ) was 27 % and 16 % in men and women , respectively . When OSAS was defined by an apnea-hypopnea index > or = 5 plus excessive daytime sleepiness , its prevalence was 4.5 % in men and 3.2 % in women . Logistic regression analyses showed that sex , body mass index , and hypertension were closely associated with the risk of SDB . Our findings show that SDB is a common problem in the Korean adult population . Underst and ing and treatment of SDB may be essential in terms of intervention to reduce the risk of related medical problems |
411 | 29,557,343 | Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction . | Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment .
Risk stratification is based on clinical - and treatment-related risk factors that do not adequately explain individual susceptibility .
The addition of genetic variants may improve risk assessment . | BACKGROUND To examine the impact of a frequent her2 gene polymorphism ( Ile655Val ) on tumor growth and on the pharmacodynamics of treatment by trastuzumab . PATIENTS AND METHODS Experimental study : The growth characteristics of cells expressing the Ile or Val isoform were examined in vitro and after injection into nude mice . The effect of trastuzumab was determined in both experimental models . Clinical study : 61 patients with advanced breast cancers and treated by trastuzumab were genotyped for HER2 by PCR-RFLP . The influence of HER2 genotype on the trastuzumab treatment was examined . RESULTS Experimental study : HER2-expressing cells acquired the characteristics of tumor cells . The Val isoform-expressing cells showed the highest growth capacity and developed aggressive tumors sensitive to trastuzumab . Clinical study : There was no link between tumor response or survival and HER2 genotype . All cases of treatment-related cardiotoxicity were found in the Ile/Val group and there was no cardiac toxicity in the Val/Val and Ile/Ile patients . CONCLUSIONS This study establishes a clear-cut difference between the two HER2 isoforms regarding their tumorogenic potential with an advantage for the Val/HER2 isoform . In breast cancer patients treated with trastuzumab , the presence of a Val allele may constitute a risk factor for cardiac toxicity Abstract The aim of this prospect i ve clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 ( CBR3p . V244 M ) and glutathione S transferase Pi ( GSTP1p . I105V ) polymorphisms . Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study . The patients ’ cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy , as well as 1 year following therapy . Gene polymorphisms were genotyped in 70 patients using TaqMan probes , vali date d by DNA sequencing . A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p . V244 M polymorphism . Patients with G-allele carriers of GSTP1p . I105V polymorphism were common ( 60 % ) , with significantly decreased PFR compared to patiens with AA genotype . Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters BACKGROUND The involvement of iron in anthracycline cardiotoxicity is supported by extensive experimental data , and by the preventive efficacy of dexrazoxane , an iron chelator . However , no clinical evidence of anthracycline-induced cardiac iron accumulation is available and the influence of previous iron overload or of genetic factors in human-induced heart disease is largely unknown . Our aim was to test the hypothesis that anthracyclines increase iron heart concentration and that HFE genotype modulates this iron deposit . METHODS We retrospectively evaluated cardiac events , cardiac iron and HFE genotype in 97 consecutive necropsies from patients with solid and hematological neoplasms . Heart and liver iron concentration was determined by atomic absorption spectroscopy . HFE gene mutations ( C282Y and H63D ) linked to hereditary hemochromatosis were analyzed by Fluorescence Resonance Energy Transfer ( FRET ) genotyping . RESULTS Heart iron concentration was increased in cases treated with a cumulative doxorubicin dose greater than 200mg/m(2 ) ( 490 vs 240 μg/g ; p=0.01 ) , independently of liver iron load or transfusion history . HFE mutated haplotypes 282C/63D ( p=0.049 ) and 282Y/63H ( p=0.027 ) were associated to higher cardiac iron deposits . The haplotype C282Y-Y/H63D-H interacted with anthracyclines for increasing cardiac iron load . In a multivariate linear regression analysis both HFE genotypes and anthracyclines contributed to heart iron concentration ( R(2)=0.284 ) . CONCLUSIONS Our data support the occurrence of an HFE-modulated heart iron accumulation in individuals treated with anthracyclines , independently of systemic iron load . If prospect ively confirmed , iron-related parameters might be useful as predictive factors for anthracycline cardiotoxicity BACKGROUND The use of anthracyclines as effective antineoplastic drugs is limited by the occurrence of cardiotoxicity . Multiple genetic variants predictive of anthracycline-induced cardiotoxicity ( ACT ) in children were recently identified . The current study was aim ed to assess replication of these findings in an independent cohort of children . PROCEDURE . Twenty-three variants were tested for association with ACT in an independent cohort of 218 patients . Predictive models including genetic and clinical risk factors were constructed in the original cohort and assessed in the current replication cohort . RESULTS . We confirmed the association of rs17863783 in UGT1A6 and ACT in the replication cohort ( P = 0.0062 , odds ratio ( OR ) 7.98 ) . Additional evidence for association of rs7853758 ( P = 0.058 , OR 0.46 ) and rs885004 ( P = 0.058 , OR 0.42 ) in SLC28A3 was found ( combined P = 1.6 × 10(-5 ) and P = 3.0 × 10(-5 ) , respectively ) . A previously constructed prediction model did not significantly improve risk prediction in the replication cohort over clinical factors alone . However , an improved prediction model constructed using replicated genetic variants as well as clinical factors discriminated significantly better between cases and controls than clinical factors alone in both original ( AUC 0.77 vs. 0.68 , P = 0.0031 ) and replication cohort ( AUC 0.77 vs. 0.69 , P = 0.060 ) . CONCLUSIONS . We vali date d genetic variants in two genes predictive of ACT in an independent cohort . A prediction model combining replicated genetic variants as well as clinical risk factors might be able to identify high- and low-risk patients who could benefit from alternative treatment options Background Anthracyclines are important chemotherapeutic agents , but their use is limited by cardiotoxicity . C and i date gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure , but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular ( LV ) function . The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy . Methods We conducted a genome-wide association study ( GWAS ) of change in LV function after anthracycline exposure in 385 patients identified from BioVU , a re source linking DNA sample s to de-identified electronic medical record data . Variants with P values less than 1 × 10−5 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospect i ve clinical trial . Pathway analysis was performed to assess combined effects of multiple genetic variants . Results Both cohorts were middle-aged adults of predominantly European descent . Among 11 c and i date loci identified in discovery GWAS , one single nucleotide polymorphism near PR domain containing 2 , with ZNF domain ( PRDM2 ) , rs7542939 , had a combined P value of 6.5 × 10−7 in meta- analysis . Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome . Identified pathways related to DNA repair , cellular metabolism , and cardiac remodeling . Conclusion Using genome-wide association we identified a novel c and i date susceptibility locus near PRDM2 . Variation in genes belonging to pathways related to DNA repair , metabolism , and cardiac remodeling may influence changes in LV function after anthracycline exposure PURPOSE This study sought to estimate cardiac dysfunction ( CD ) risk for patients receiving trastuzumab ; to characterize observed CD by severity , treatment , and clinical outcome ; to assess effects of baseline clinical risk factors on CD ; and to assess effects of cumulative doses of anthracyclines and trastuzumab on CD . PATIENTS AND METHODS A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumab clinical trials was performed . Predefined criteria were used for the diagnosis , and the New York Heart Association functional classification system was used to document CD severity . Product-limit estimates were used to summarize the cumulative anthracycline and trastuzumab doses at the time of CD onset . RESULTS Patients treated with trastuzumab were found to be at an increased risk for CD . The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide ( 27 % ) . The risk was substantially lower in patients receiving paclitaxel and trastuzumab ( 13 % ) or trastuzumab alone ( 3 % to 7 % ) ; however , most of these patients had received prior anthracycline therapy . CD was noted in 8 % of patients receiving anthracycline plus cyclophosphamide and 1 % receiving paclitaxel alone . Most trastuzumab-treated patients developing CD were symptomatic ( 75 % ) , and most improved with st and ard treatment for congestive heart failure ( 79 % ) . CONCLUSION Trastuzumab is associated with an increased risk of CD , which is greatest in patients receiving concurrent anthracyclines . In most patients with metastatic breast cancer , the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab The purpose of this study was to investigate , in the context of a prospect i ve node-positive-breast cancer trial HER2 containing-regimen ( UNICANCER-PACS 04 trial ) , the predictive value of HER2 , FCGRIIA , and FCGRIIIA gene polymorphisms for cardiac toxicity and efficacy of trastuzumab . We analyzed HER2–I655V , FCGR2A – H131R , and FCGR3A – V158F single nucleotide polymorphisms in patients in adjuvant setting treated by six courses of either fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 , or epirubicin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks then r and omly assigned , in case of HER2 overexpressing tumor , to either trastuzumab for 1 year or nothing . Left ventricular ejection fraction and clinical examination were monitored in each patient , seven times throughout the study to detect congestive heart failure or asymptomatic sub clinical cardiac toxicity . All genotypes were analyzed in relation to cardiac toxicity , EFS , and OS . One hundred and thirty-two HER2-positive breast cancer patients were analyzed . The HER2–I655V genotype was significantly associated with cardiac toxicity ( p = 0.025 ) . The FCGR2A-131 H/H genotype was significantly correlated with a shorter EFS ( p = 0.027 ) . The FCGR3A-158 V/V genotype was not correlated with EFS nor OS . These results might be useful in making a treatment choice of HER2 blockers in adjuvant setting by with an increase in efficacy and decrease in toxicity IMPORTANCE This is the first r and omized placebo-controlled evaluation of a medical intervention for the prevention of trastuzumab-related cardiotoxic effects . OBJECTIVE To determine as the primary end point whether angiotensin II antagonist treatment with c and esartan can prevent or ameliorate trastuzumab-related cardiotoxic effects , defined as a decline in left ventricular ejection fraction ( LVEF ) of more than 15 % or a decrease below the absolute value 45 % . DESIGN This r and omized , placebo-controlled clinical study was conducted between October 2007 and October 2011 in 19 hospitals in the Netherl and s , enrolling 210 women with early breast cancer testing positive for human epidermal growth factor receptor 2 ( HER2 ) who were being considered for adjuvant systemic treatment with anthracycline-containing chemotherapy followed by trastuzumab . INTERVENTIONS A total of 78 weeks of c and esartan ( 32 mg/d ) or placebo treatment ; study treatment started at the same day as the first trastuzumab administration and continued until 26 weeks after completion of trastuzumab treatment . MAIN OUTCOMES AND MEASURES The primary outcome was LVEF . Secondary end points included whether the N-terminal of the prohormone brain natriuretic peptide ( NT-proBNP ) and high-sensitivity troponin T ( hs-TnT ) can be used as surrogate markers and whether genetic variability in germline ERBB2 ( formerly HER2 or HER2/neu ) correlates with trastuzumab-related cardiotoxic effects . RESULTS A total of 206 participants were evaluable ( mean age , 49 years ; age range , 25 - 69 years ) 103 in the c and esartan group ( mean age , 50 years ; age range , 25 - 69 years ) and 103 in the placebo group ( mean age , 50 years ; age range , 30 - 67 years ) . Of these , 36 manifested at least 1 of the 2 primary cardiac end points . There were 3.8 % more cardiac events in the c and esartan group than in the placebo group ( 95 % CI , -7 % to 15 % ; P = .58 ) : 20 events ( 19 % ) and 16 events ( 16 % ) , respectively . The 2-year cumulative incidence of cardiac events was 0.28 ( 95 % CI , 0.13 - 0.40 ) in the c and esartan group and 0.16 ( 95 % CI , 0.08 - 0.22 ) in the placebo group ( P = .56 ) . C and esartan did not affect changes in NT-proBNP and hs-TnT values , and these biomarkers were not associated with significant changes in LVEF . The Ala1170Pro homozygous ERBB2 genotype was associated with a lower likelihood of the occurrence of a cardiac event compared with Pro/Pro + Ala/Pro genotypes in multivariate analysis ( odds ratio , 0.09 ; 95 % CI , 0.02 - 0.45 ; P = .003 ) . CONCLUSIONS AND RELEVANCE The findings do not support the hypothesis that concomitant use of c and esartan protects against a decrease in left ventricular ejection fraction during or shortly after trastuzumab treatment in early breast cancer . The ERBB2 germline Ala1170Pro single nucleotide polymorphism may be used to identify patients who are at increased risk of trastuzumab-related cardiotoxic effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00459771 Background — Three types of anthracycline-induced cardiotoxicities are currently recognized : acute , early-onset chronic , and late-onset chronic . However , data supporting this classification are lacking . We prospect ively evaluated incidence , time of occurrence , clinical correlates , and response to heart failure therapy of cardiotoxicity . Methods and Results — We assessed left ventricular ejection fraction ( LVEF ) , at baseline , every 3 months during chemotherapy and for the following year , every 6 months over the following 4 years , and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy . In case of cardiotoxicity ( LVEF decrease > 10 absolute points , and < 50 % ) , heart failure therapy was initiated . Recovery from cardiotoxicity was defined as partial ( LVEF increase > 5 absolute points and > 50 % ) or full ( LVEF increase to the baseline value ) . The median follow-up was 5.2 ( quartile 1 to quartile 3 , 2.6–8.0 ) years . The overall incidence of cardiotoxicity was 9 % ( n=226 ) . The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 ( quartile 1 to quartile 3 , 3–6 ) months . In 98 % of cases ( n=221 ) , cardiotoxicity occurred within the first year . Twenty-five ( 11 % ) patients had full recovery , and 160 ( 71 % ) patients had partial recovery . At multivariable analysis , end-chemotherapy LVEF ( hazard ratio , 1.37 ; 95 % confidence interval , 1.33–1.42 for each percent unit decrement ) and cumulative doxorubicin dose ( hazard ratio , 1.09 ; 95 % confidence interval , 1.04–1.15 for each 50 mg/m2 increment ) were independent correlates of cardiotoxicity . Conclusions — Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment . Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function Cardiomyopathy has been recognized as a complication after hematopoietic cell transplantation ( HCT ) . Using a nested case-cohort design , we examined the relationships between demographic , therapeutic , and selected cardiovascular disease risk factors among ≥1-year HCT survivors who developed cardiomyopathy before ( n = 43 ) or after ( n = 89 ) 1 year from HCT as compared to a r and omly selected subcohort of survivors without cardiomyopathy ( n = 444 ) . Genomic data were available for 79 cases and 267 noncases . Clinical and genetic covariates were examined for association with the risk of early or late cardiomyopathy . Clinical risk factors associated with both early- and late-onset cardiomyopathy included anthracycline exposure ≥250 mg/m(2 ) and pre-existing hypertension . Among late-onset cardiomyopathy cases , the development of diabetes and ischemic heart disease further increased risk . We replicated several previously reported genetic associations among early-onset cardiomyopathy cases , including rs1786814 in CELF4 , rs2232228 in HAS3 , and rs17863783 in UGT1A6 . None of these markers were associated with risk of late-onset cardiomyopathy . A combination of demographic , treatment , and clinical covariates predicted early-onset cardiomyopathy with reasonable accuracy ( area under the curve [ AUC ] , .76 ; 95 % confidence interval [ CI ] , .68 to .83 ) , but prediction of late cardiomyopathy was poor ( AUC , .59 ; 95 % CI .53 to .67 ) . The addition of genetic polymorphisms with marginal associations ( odds ratios ≥1.3 ) did not enhance prediction for either early- or late-onset cardiomyopathy . Conventional cardiovascular risk factors influence the risk of both early- and late-onset cardiomyopathy in HCT survivors . Although certain genetic markers may influence the risk of early-onset disease , further work is required to vali date previously reported findings and to determine how genetic information should be incorporated into clinical ly useful risk prediction models Purpose : Anthracycline-induced congestive heart failure ( CHF ) is a rare but serious toxicity associated with this commonly employed anticancer therapy . The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient . Herein , we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline . Experimental Design : We performed a genome-wide association study in 3,431 patients from the r and omized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism ( SNP ) genotypes associated with an increased risk of anthracycline-induced CHF . We further attempted c and i date validation in two independent phase III adjuvant trials , E1199 and BEATRICE . Results : When evaluating for cardiologist-adjudicated CHF , 11 SNPs had a P value < 10−5 , of which nine independent chromosomal regions were associated with increased risk . Validation of the top two SNPs in E1199 revealed one SNP rs28714259 that demonstrated a borderline increased CHF risk ( P = 0.04 , OR = 1.9 ) . rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction ( P = 0.018 , OR = 4.2 ) . Conclusions : rs28714259 represents a vali date d SNP that is associated with anthracycline-induced CHF in three independent , phase III adjuvant breast cancer clinical trials . Clin Cancer Res ; 23(1 ) ; 43–51 . © 2016 AACR |
412 | 12,890,083 | A wide variety of intervention strategies were reported .
The most common interventions were self-monitoring , general health education , goal setting , supervised center-based exercise , problem solving , feedback , reinforcement , and relapse prevention education .
Common method ological weaknesses included small sample s , untested outcome measures , and time-limited longitudinal design s. Significant numbers of aging adults increased their physical activity in response to experimental interventions .
The amount of increased activity rarely equaled accepted behavior st and ards to achieve positive health outcomes . | This paper review s r and omized , controlled trials ( RCTs ) that have attempted to increase physical activity behavior by aging adults .
A systematic review was necessary because numerous studies target older adults , and previous review s have addressed a limited range of primary studies . | OBJECTIVES This study evaluated the effectiveness ( changes in health behaviors , health status , and health service utilization ) of a self-management program for chronic disease design ed for use with a heterogeneous group of chronic disease patients . It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities . METHODS The study was a six-month r and omized , controlled trial at community-based sites comparing treatment subjects with wait-list control subjects . Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease , lung disease , stroke , or arthritis . Health behaviors , health status , and health service utilization , as determined by mailed , self-administered question naires , were measured . RESULTS Treatment subjects , when compared with control subjects , demonstrated improvements at 6 months in weekly minutes of exercise , frequency of cognitive symptom management , communication with physicians , self-reported health , health distress , fatigue , disability , and social/role activities limitations . They also had fewer hospitalizations and days in the hospital . No differences were found in pain/physical discomfort , shortness of breath , or psychological well-being . CONCLUSIONS An intervention design ed specifically to meet the needs of a heterogeneous group of chronic disease patients , including those with comorbid conditions , was feasible and beneficial beyond usual care in terms of improved health behaviors and health status . It also result ed in fewer hospitalizations and days of hospitalization OBJECTIVE To assess the efficacy of physical activity promotion in primary care office setting s. DESIGN Systematic review of clinical trials in which the efficacy of physical activity promotion was investigated in a primary care office setting with at least one month of follow up . SUBJECTS A total of 13,981 adults , aged 17 - 85 + , were included from 203 practice s in eight trials assessing physical activity promotion in primary care office setting s. MAIN OUTCOME MEASURES Odds ratios and 95 % confidence intervals were calculated comparing the number of participants who increased their physical activity or were active at follow up in the intervention group with a control group for each study . RESULTS Five of eight trials where positive with statistically significant results ( range 0.91 - 6.56 ) , but significant biases or limited clinical relevance of the outcomes were found in all trials . Short term trials of less than one year ( four of four were positive ) , single-risk-factor trials ( three of three were positive ) , r and omised clinical trials ( two of three were positive ) , and those assessing moderate levels of physical activity ( three of four were positive ) were most likely to find benefit . Only one of four trials lasting longer than a year were positive . CONCLUSION There is limited evidence from well design ed trials that office based physical activity promotion in primary care setting s is efficacious in promoting changes in physical activity that could conceivably have lasting clinical benefits We performed a r and omized controlled trial to evaluate the effectiveness of a patient education and health promotion program in the treatment of Parkinson 's disease . The health promotion program ( PROPATH ) was design ed to improve health confidence , provide information and support , improve physical function through exercise , and work with the physician to optimize medical treatment and compliance . The intervention was delivered by mail , with disease assessment question naires completed by patient or caregiver at 0 , 2 , 4 , and 6 months , with computer-generated reports and individualized recommendation letters returned to patients and reports to physicians . Two hundred ninety patients completed the 6-month trial , 140 patients in the intervention group and 150 in a control group of patients who received only question naires . The intervention group had significantly increased exercise , decreased " time off " and percentage of time off , reduced side effects , and decreased summary Parkinson 's scores by approximately 10 % ( P > 0.05 ) . Twelve of 13 variables showed differences favoring the intervention group . The rate of progression of summary scores became essentially flat during the program for the intervention group and continued to rise sharply for controls ( P > 0.01 ) . Levodopa dose rose for controls and slightly decreased for the intervention group . Doctor visits , hospital days , and sick days were reduced in the intervention group . The quality -of-life assessment demonstrated improvement in patient global , self-efficacy scores , and spouse or caregiver assessment s. We conclude that a low-cost patient education program provides a useful adjunct to medical therapy of Parkinson 's disease , may reduce costs , and can improve intermediate term outcomes BACKGROUND The U.S. Congress m and ated evaluations , initiated in 1989 , to determine whether extending Medicare benefits to include preventive services would improve health status , reduce costs of care , and improve health risk behaviors of beneficiaries . METHODS The Johns Hopkins Medicare Preventive Services Demonstration was a r and omized trial in which Medicare beneficiaries were assigned either to an intervention group that was offered yearly preventive visits for 2 years and optional counseling visits to their primary care provider or to a control group that received usual care . This report describes the effect of the intervention over a period of 2 years on smoking , problem alcohol use , and sedentary lifestyle . RESULTS Differences were observed between the intervention and control groups in the extent to which changes occurred in smoking and problem alcohol use , but none of the differences was statistically significant . The proportion of smokers who quit was higher in the intervention group than in the control group ( 24.2 vs 17.9 % , P = 0.09 ) . However , a higher proportion of problem drinkers in the control group improved ( 67.1 vs 57.0 % , P = 0.183 ) . There was virtually no difference between the intervention and the control groups in the proportion with improvement in sedentary lifestyle . CONCLUSIONS This study demonstrates the difficulty of bringing about health behavior change in older patients in the course of a yearly preventive visit for 2 years with their primary care physician when the visit encompasses screening and immunizations , as well as health behavior counseling directed by the physician . Further study is required to determine whether a more intense program of counseling for health behavior change among older persons by their primary care providers would be effective Abstract Objectives : To establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients . Design : R and omised controlled trial with 1 year follow up . Setting : Metropolitan general practice s in Melbourne , Australia . Subjects : 42 general practitioners and 267 of their patients aged over 65 years . Intervention : Educational and clinical practice audit programme for general practitioners on health promotion for elderly people . Main outcome measures : Patients ' physical activity , functional status , self rated health , immunisation status , social contacts , psychological wellbeing , drug usage , and rate of influenza vaccination . Primary efficacy variables were changes in outcome measures over 1 year period . Results : Patients in the intervention group had increased ( a ) walking by an average of 88 minutes per fortnight , ( b ) frequency of pleasurable activities , and ( c ) self rated health compared with the control group . No change was seen in drug usage , rate of influenza vaccination , functional status , or psychological wellbeing as a result of the intervention . Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22 % if activity was sustained for 5 years . Conclusions : Education of the general practitioners had a positive effect on health outcomes of their elderly patients . General practitioners may have considerable public health impact in promotion of health for elderly patients . Key messages Few educational interventions for doctors have shown benefit to the health of patients Elderly people were identified in the UK health initiatives as in need of additional attention , and levels of health protective behaviours were low in community surveys A multifaceted educational intervention for general practitioners was effective in improving walking behaviour , self rated health status , and the frequency of social contacts in elderly patients General practitioners are effective in improving health and health behaviours in their elderly The medical care system is not very effective in modifying health behavior of individuals , in particular , ensuring patient compliance with medication regimens , healthy diets , regular physical activity , and regular health screening , and in the avoidance of substance abuse . Telephone-Linked Care ( TLC ) is a telecommunications technology that enables computer-controlled telephone counseling with patients in their homes . It has been applied to the task of improving a number of different health behaviors . R and omized controlled studies suggest that use of the system for as little as 3 months is associated with improvement in adherence to medication regimens , dietary change in hypercholesterolemia , and increased physical activity among sedentary individuals . Future work involves applying the technology to other important health behaviors , optimally using health behavior theory in the system design , targeting use of TLC to the most appropriate patient groups , incorporating new computer and telecommunications technology into the system , and interfacing TLC into the health care delivery system This study investigated the aerobic fitness , body composition , spirometric variables , Human Activity Profile , and level of adherence to physical activity subsequent to completion of a progressive walking program of six month 's duration ( T1 ) . Sixty-six women previously r and omized to training ( TG ) and control ( CG ) groups were reassessed six months after finishing the six month walking program ( T2 ) . During the follow-up period , 77.8 % of the TG subjects continued with exercise and maintained lower ( p < 0.005 ) exercise heart rates compared to the CG . A Mann-Whitney U test on the difference scores ( T2-T1 ) revealed no difference ( p > 0.05 ) between the TG and CG for changes in Maximum Current Activity and Normative Impairment Index , which are both components of the Human Activity Profile , with the earlier increases ( p < 0.05 ) in these parameters by the TG having been maintained . Participation in a previous low frequency training regimen therefore result ed in elderly women adopting and sustaining a higher level of habitual physical activity . This is important because a favorable modification of lifestyle factors is likely to be indicative of an enhanced outlook for independence This study examines the longitudinal ( 48 months ) effects of a preventive services intervention trial with Medicare beneficiaries . The health promotion intervention incorporated a series of workshops and targeted individualized counseling dealing primarily with nutrition and exercise . All subjects completed a health risk appraisal ( HRA ) question naire , which served as a dependent measure . Results show significant , positive changes in intervention subjects in two activity outcomes , aerobic activity and stretching exercises . Although previous research on this cohort found significant positive changes in nutrition behaviors at 12-month follow-up , these differences were not sustained over the three-year follow-up period . The results offer encouragement that continued research on health promotion will eventually produce protocol s for select activities that will improve the status of seniors ' health BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age , little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken . METHODS One hundred three adults age 65 years and older , recruited via population -based methods , were r and omized to 12 months of community-based , moderate-intensity endurance and strengthening exercises ( Fit & Firm ) or stretching and flexibility exercises ( Stretch & Flex ) . A combination of class- and home-based exercise formats was used . Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention . RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects . Stretch & Flex subjects reported greater improvements in bodily pain , and Stretch & Flex men evidence d greater improvements in flexibility relative to Fit & Firm subjects . Although overall exercise adherence was high in both exercise conditions ( approximately 80 % ) , subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions . CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes . This represents one of the first studies to report significant improvements in an important quality of life outcome -bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults OBJECTIVE To determine whether gains in functioning observed immediately following participation in an 8-week program of supervised fitness walking for patients with knee osteoarthritis were sustained at 1-year followup . METHODS Twenty-nine ( 61.1 % ) of 47 original intervention program patients and 23 ( 51.1 % ) of 45 original control patients were interviewed by telephone at 1-year followup . Patients completed the Arthritis Impact Measurement Scales physical activity , arthritis impact , pain , medication use , and general health perceptions subscales , as well as a separate visual analog pain scale and measures of perceived self-efficacy to cope with arthritis pain and other symptoms . RESULTS Adherence to walking was low , and there were no statistically significant differences between intervention and control patients at one year . CONCLUSIONS The failure of intervention patients to maintain regular walking result ed in loss of functional benefits that were observed at 8 weeks in the original study . Long-term adherence to walking is critical to maintenance of initial gains in functional outcomes Higher levels of physical activity are associated with lower risk of cardiovascular disease . There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation . In this study , the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population . Data obtained in 1989 - 1990 and 1992 - 1993 from the Cardiovascular Health Study , a cohort of 5,888 men and women aged > /=65 years , were analyzed . Concentrations of the inflammation markers-C-reactive protein , fibrinogen , Factor VIII activity , white blood cells , and albumin-were compared cross-sectionally by quartile of self-reported physical activity . Compared with persons in the lowest quartile , those in the highest quartile of physical activity had 19 % , 6 % , 4 % , and 3 % lower concentrations of C-reactive protein , white blood cells , fibrinogen , and Factor VIII activity , respectively , after adjustment for gender , the presence of cardiovascular disease , age , race , smoking , body mass index , diabetes , and hypertension . Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose . There was no association between physical activity and albumin . Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort . These data suggest that increased exercise is associated with reduced inflammation . Prospect i ve studies will be required for verification of these findings There is ample evidence of the benefits of exercise for older people . Less is known about the most effective strategies for promoting the participation of older people in exercise regimes . An approach whereby practice nurses used motivational interviewing , based on Prochaska and Di Clemente 's model of behaviour change , was piloted in two general practice s. The strategy appeared feasible and will be tested further in a large controlled trial BACKGROUND Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community . OBJECTIVE To evaluate the impact of a 1-year , senior center-based chronic illness self-management and disability prevention program on health , functioning , and healthcare utilization in frail older adults . DESIGN A r and omized controlled trial . SETTING A large senior center located in a northeast Seattle suburb . The trial was conducted in collaboration with primary care providers of two large managed care organizations . PARTICIPANTS A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practice s. INTERVENTION A targeted , multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner ( GNP ) . MEASUREMENTS Self-reported Physical function , physical performance tests , health care utilization , and health behaviors . RESULTS Each of 101 intervention participants met with the GNP from 1 to 8 times ( median = 3 ) during the study year . The intervention group showed less decline in function , as measured by disability days and lower scores on the Health Assessment Question naire . Other measures of function , including the SF-36 and a battery of physical performance tests , did not change with the intervention . The number of hospitalized participants increased by 69 % among the controls and decreased by 38 % in the intervention group ( P = .083 ) . The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls ( total days = 33 vs 116 , P = .049 ) . The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications . CONCLUSIONS This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults . Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice |
413 | 22,883,473 | It is undesirable to expect 100 % treatment coverage for depression , given many will remit before access to services is feasible .
Considering reported rates of spontaneous remission , a short untreated period seems defensible for this sub population , where judged appropriate by the clinician .
Conclusions may not apply to individuals with more severe depression | BACKGROUND Few studies have examined spontaneous remission from major depression .
This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a year , and whether remission rates vary by disorder severity . | The authors evaluated a six-session interactive computer cognitive-behavioral treatment program given to volunteer patients who met Research Diagnostic Criteria ( RDC ) for major or minor depressive disorder . Patients were r and omly assigned to computer-administered cognitive-behavioral treatment , to therapist-administered cognitive-behavioral treatment , or to a waiting-list control condition . After treatment and at 2-month follow-up , both treatment groups had improved significantly more than control subjects in their scores on the Beck Depression Inventory , SCL-90-R depression and global scales , Hamilton Rating Scale for Depression , and Automatic Thoughts Question naire . The treatment groups did not differ from each other at either time OBJECTIVE To design a treatment manual and adherence measure for attachment-based family therapy ( ABFT ) for adolescent depression and to collect pilot data on the treatment 's efficacy . METHOD Over a period of 2 years , 32 adolescents meeting criteria for major depressive disorder ( MDD ) were r and omly assigned to 12 weeks of ABFT or a 6-week , minimal-contact , waitlist control group . The sample was 78 % female and 69 % African American ; 69 % were from low-income , inner-city communities . RESULTS At post-treatment , 81 % of the patients treated with ABFT no longer met criteria for MDD , in contrast with 47 % of patients in the waitlist group . Mixed factorial analyses of variance revealed that , compared with the waitlist group , patients treated with ABFT showed a significantly greater reduction in both depressive and anxiety symptoms and family conflict . Of the 15 treated cases assessed at the follow-up , 13 patients ( 87 % ) continued to not meet criteria for MDD 6 months after treatment ended . CONCLUSIONS ABFT appears to be a promising treatment and worthy of further development Les auteurs ont trouve une efficacite semblable pour la therapie cognitivo-comportementale et pour la relaxation , dans le traitement de la depression chez In this study , the authors examined prospect ively the 24-month natural course of remission from major depressive disorder ( MDD ) as a function of personality disorder ( PD ) comorbidity . In 302 participants ( 196 women , 106 men ) , psychiatric and PDs were assessed at baseline with diagnostic interviews , and the course of MDD was assessed with the Longitudinal Interval Follow-Up Evaluation at 6- , 12- , and 24-month follow-ups . Survival analyses revealed an overall 24-month remission rate of 73.5 % for MDD that differed little by gender . Participants with MDD who had certain forms of coexisting PD psychopathology ( schizotypal , borderline , or avoidant ) as their primary PD diagnoses had a significantly longer time to remission from MDD than did patients with MDD without any PD . These PDs emerged as robust predictors of slowed remission from MDD even when controlling for other negative prognostic predictors OBJECTIVE The purpose of this study was to assess the differences between early ( EDs ) , late drop-outs ( LDs ) and completers in the continuation phase of a clinical trial . METHODS The authors studied 119 out patients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day , and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy ( CBT ) . Patients were assessed using the Structured Clinical Interview for DSM-III-R-Axis I ( SCID-Patient Edition ) , Hamilton Depression Rating Scale ( HAMD-17 ) and the following self-rated scales : Beck Depression Inventory ( BDI ) , Beck Hopelessness Scale ( BHS ) , Anxiety Sensitivity Index ( ASI ) and the Symptom Question naire ( SQ ) prior to starting the 26-week continuation phase . We defined ' EDs ' as patients who dropped out either at or prior to Visit 2 ( which was at 2 months into the 6-month continuation phase ) ; those dropping out at Visit 3 or later were defined as ' LDs ' ( ED < or = 2 months and LD > 2 months ) . The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis . RESULTS Of the 119 out patients , 83 were completers ( mean age : 42.1 + /- 9.0 years , 46 [ 55 % ] women , age of onset of major depressive disorder [ MDD ] = 24.3 + /- 12.5 years ) , 11 were EDs ( mean age : 38.1 + /- 13.0 years , 4 [ 36 % ] women , age of onset of MDD = 22.0 + /- 11.1 years ) and 25 were LDs ( mean age : 35.2 + /- 10.4 years , 12 [ 48 % ] women , age of onset of MDD = 24.6 + /- 11.6 years ) . LDs were significantly younger than completers ( P<.01 ) . There was no significant difference in age between EDs and LDs , nor between EDs and completers . EDs and completers were depressed for a longer period of time compared to LDs ( P<.05 ) . EDs also had significantly greater overall impairment in social adjustment compared to completers ( P<.05 ) . CONCLUSIONS Our data suggest that LDs are significantly younger than completers , although age is not a predictor between EDs and LDs . Further , EDs and completers are depressed for a longer duration than LDs , and EDs have significantly greater social impairment compared to completers . Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial OBJECTIVE This paper presents retrospective and prospect i ve data regarding time course parameters of major depressive disorder ( MDD ) in community adolescents ( 14 to 18 years old ) : time to onset and recovery and , among those who recovered , time to recurrence . METHOD Diagnostic interviews were conducted with 1,508 r and omly selected high school students . Three hundred sixty-two had experienced at least one past or current episode of MDD . RESULTS Mean age at onset of first episode was 14.9 ( SD = 2.8 ) . Early MDD onset was associated with female gender and suicidal ideation . MDD episode duration ranged from 2 to 520 weeks , with a mean of 26.4 weeks ( SE = 3.3 ) and a median of 8.0 weeks . Longer episodes were observed in those whose depression occurred early ( at or before age 15 ) , whose depression had been accompanied by suicidal ideation , and for whom treatment was sought . Of the adolescents who recovered , 5 % relapsed within 6 months , 12 % within 1 year , and approximately 33 % within 4 years . Shorter time to recurrence was associated with prior suicidal ideation and attempt and with later first onset . CONCLUSIONS Risk of MDD is low in childhood , increasing substantially with adolescence . The majority of episodes in community adolescents are relatively brief , although the risk of recurrence is substantial . Suicidal behaviors are important mediators of episode duration and of recurrence The objectives of the present report were : a ) to determine the spontaneous remission rate in depressed out patients who do not receive antidepressant medication ; b ) to develop a novel method for obtaining a control group that can be used to gauge the effectiveness of antidepressant medication in clinical practice ; and c ) to compare response rates from the present sample with outcomes of depressed patients in our practice who were treated with antidepressant medications . By using a naturalistic design , prospect i ve assessment s were made on all depressed out patients . Twenty-five patients who met full criteria for a major depressive episode ended up not taking antidepressant medication for a variety of reasons . " Response " rates to a no-treatment trial were determined with st and ard outcome criteria using the Clinical Global Impression-Improvement scale . Eight patients ( 32.0 % ) had a positive response , 5 patients ( 20.0 % ) had a partial response , and 12 patients ( 48.0 % ) were nonresponders to a no-treatment trial . These response rates were higher than expected , but significantly lower than what we had found in a cohort of depressed patients who underwent an antidepressant trial ( p = .02 ) . Likewise , treatment-resistant patients fared better on pharmacotherapy , though this difference was not statistically significant . These results suggest that the occurrence of spontaneous remissions may be common in clinical practice , and therefore the specific short-term benefits of antidepressant medication in clinical practice may frequently be overestimated . Despite the high rate of spontaneous remission in our sample , the present study allowed us to confirm the effectiveness of antidepressant medication in clinical practice using a novel method for obtaining a control comparison group Compared the effects of 2 psychotherapies based on divergent conceptualizations of depression in later life . Seventy-five older adults diagnosed with major depressive disorder were assigned r and omly to problem-solving therapy ( PST ) , reminiscence therapy ( RT ) , or a waiting-list control ( WLC ) condition . Participants in PST and RT were provided with 12 weekly sessions of group treatment . Dependent measures , taken at baseline , posttreatment , and 3-month follow-up , included self-report and observer-based assessment s of depressive symptomatology . At posttreatment , both the PST and the RT conditions produced significant reductions in depressive symptoms , compared with the WLC group , and PST participants experienced significantly less depression than RT subjects . Moreover , a significantly greater proportion of participants in PST versus RT demonstrated sufficient positive change to warrant classification of their depression as improved or in remission at the posttreatment and follow-up evaluations Elementary school children with mild-to-moderate depressive symptoms were r and omly assigned to a control group or an 8-session Primary and Secondary Control Enhancement Training program . The program focused on ( a ) primary control ( changing objective conditions to fit one 's wishes ; e.g. , through activity selection and goal attainment ) and ( b ) secondary control ( changing oneself to buffer the impact of objective conditions ; e.g. , altering depressogenic thinking , practicing mood-enhancing cognitions ) . At immediate posttreatment and 9-month follow-up , the treatment group showed greater reductions than the control group in depressive symptomatology on the Children 's Depression Inventory and the Revised Children 's Depression Rating Scale , and treated children , more than controls , shifted from above to within the normal range on both measures . Future research is needed to test treatment effects with severely depressed youths BACKGROUND We evaluated the long-term outcome of depression and anxiety and associated disability among primary -care attenders with common psychiatric disorders and symptoms ( n = 201 ) using binary and multicategorical , interview-based outcome measures of psychiatric illness and disability . METHODS A two-stage design was used . In the first stage , 1994 consecutive attenders of 25 general practitioners were screened on psychiatric illness with the General Health Question naire and by their physicians . A stratified r and om sample ( n = 292 ) with differing probabilities was selected for second-stage interview ( Present State Examination and Groningen Disability Schedule ) . Patients with psychiatric symptoms ( n = 201 ) were reassessed 1 ( n = 182 ) and 3 1/2 ( n = 154 ) years later . RESULTS At 1- and 3 1/2-year follow-ups , many cases no longer met the criteria of their baseline diagnosis and disability levels had substantially dropped . However , partial remission , not full recovery , was the rule , and was associated with residual disability . Depression had better outcomes than anxiety and mixed anxiety-depression . CONCLUSIONS We concluded that a multicategorical , rather than a binary , outcome measure better reflects patient outcomes , since it highlights partial remission , mild symptoms , and residual disability , and as such , stresses the need to supplement short-term treatment . A multicategorical caseness model may be advantageous for research and clinical practice . We suggest a dynamic-equilibrium model to account for residual symptoms and disability . This study is a follow-up to two earlier reports on the recognition , treatment , and 1-year course of common psychiatric illnesses in general practice The goal of the study was to describe the naturalistic course of unipolar major depression in subjects not receiving somatic therapy for their depressive illness . Affectively ill individuals were recruited into the Collaborative Depression Study and followed prospect ively for up to 15 years . One hundred thirty subjects who recovered from their intake episode of major depression subsequently experienced a recurrence that went untreated for at least 4 weeks following onset of the recurrence . The duration of the recurrent episode was examined using survival analytic techniques . Of the 130 subjects , 46 obtained somatic therapy at some time during the course of their depressive illness , while 84 subjects received no somatic therapy throughout their entire depressive episode . Survival analysis , which accounts for these 46 individuals by censoring their episodes at the time treatment was obtained , yielded a median time to recovery of 23 weeks . In the sub sample of 84 subjects whose depressive illness went untreated from its inception through its resolution , the median time to recovery was 13 weeks . These results suggest that there is a high rate of recovery in individuals not receiving somatic treatment of their depressive illness , particularly in the first 3 months of an episode . Because treatment-seeking behavior is known to be associated with a worse prognosis , 23 weeks probably represents a lower-limit approximation of the median duration of an untreated depressive episode OBJECTIVE This trial examined the effects of both acute and maintenance cognitive-behavioral therapy ( CBT ) for depressed adolescents . METHOD Adolescents with major depression or dysthymia ( N = 123 ) were r and omly assigned to 1 of 3 eight-week acute conditions : adolescent group CBT ( 16 two-hour sessions ) ; adolescent group CBT with a separate parent group ; or waitlist control . Subsequently , participants completing the acute CBT groups were r and omly reassigned to 1 of 3 conditions for the 24-month follow-up period : assessment s every 4 months with booster sessions ; assessment s only every 4 months ; or assessment s only every 12 months . RESULTS Acute CBT groups yielded higher depression recovery rates ( 66.7 % ) than the waitlist ( 48.1 % ) , and greater reduction in self-reported depression . Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different . Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression . The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase . CONCLUSIONS The findings , which replicate and exp and upon a previous study , support the growing evidence that CBT is an effective intervention for adolescent depression This study examined the effect of a cognitive behavior therapy ( CBT ) therapy intervention design ed to reduce depression in older patients with elevated cardiovascular disease ( CVD ) risk . Forty‐eight depressed patients with elevated CVD were r and omized to a 16‐week individual CBT intervention ( n = 23 ) or a wait‐list control ( WLC ) group ( n = 25 ) . Pre‐ and post‐treatment measures of depression were obtained during office visits , and measures of positive and negative affect were obtained during laboratory psychological stress testing and at five points during the day . At post‐treatment , the CBT subjects were significantly less depressed than WLC subjects on the Hamilton Depression Inventory ( F = 52.8 , P<.001 , ES = 1.85 ) and the Beck Depression Inventory ( F = 17.1 , P = < .001 , ES = 0.85 ) . Fifty‐seven percent ( 13/23 ) of subjects in the CBT treatment were considered to be in remission ( on the basis of a clinical interview ) at post compared to only 4 % ( 1/25 ) in the WLC ( χ2 = 9.0 , P = .003 ) . Treatment subjects reported significantly less stress on the Perceived Stress Scale ( F = 23.2 , P<.001 ) . CBT significantly improved mean positive affect during the day ( F = 12.7 , P = .0001 ) but there were no significant differences in mean negative affect ( F = 1.8 , P = .19 ) . CBT significantly reduced negative affect ( F = 7.1 , P = .01 ) during psychological stress testing but did not affect positive affect . CBT is an effective treatment for reducing depression and increasing positive affect in patients at risk for CVD , but the results vary by time of measurement and measurement setting . Depression and Anxiety 0:1–10 , 2007 . Published 2007 Wiley‐Liss , OBJECTIVE To assess the efficacy of acupuncture as an intervention for major depressive disorder ( MDD ) . METHOD Acupuncture was examined in 151 patients with MDD ( DSM-IV ) who were r and omly assigned to 1 of 3 groups in a double-blind r and omized controlled trial . The specific intervention involved Traditional Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression ; the control conditions consisted of ( 1 ) a nonspecific intervention using a comparable number of legitimate acupuncture points not specifically targeted to depressive symptoms and ( 2 ) a waitlist condition , which involved waiting without intervention for 8 weeks . After 8 weeks , all patients received the depression-specific acupuncture . Each 8-week intervention regimen consisted of 12 acupuncture sessions delivered in an acupuncturist 's office in the community . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression . The study was conducted from February 1998 to April 2002 . RESULTS Twenty patients terminated treatment before the completion of the 8-week intervention ( 13 % ) but not differentially by study group . R and om regression models of the intent-to-treat sample revealed that although patients receiving acupuncture improved more than those awaiting intervention , no evidence of differential efficacy of the depression-specific over nonspecific intervention was found . Response rates in acupuncture-treated patients were relatively low after 8 weeks ( 22 % and 39 % for specific and nonspecific intervention groups , respectively ) , with the response rate after the entire 16-week trial reaching 50 % . CONCLUSION Although TCM manual acupuncture is a well-tolerated intervention , results fail to support its efficacy as a monotherapy for MDD . It ca n't be ruled out that factors unique to the implementation of acupuncture in this research study may have limited the efficacy of interventions compared to those provided in naturalistic setting s. CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00010517 OBJECTIVE To determine how primary care physicians treat patients with major depression in the course of routine practice and the degree to which such practice produces outcomes anticipated with interventions recommended by the Agency for Health Care Policy and Research Depression Guideline Panel . DESIGN S Prospect i ve cohort study . SETTING S Academically affiliated ambulatory family practice centers and internal medicine clinics in urban neighborhoods of Pittsburgh , Pa. PATIENTS Ninety-two patients who were seen in primary care practice s and who met criteria for a current major depression as determined by the Diagnostic Interview Schedule and a psychiatrist 's assessment . INTERVENTION Physicians were informed of the patient 's psychiatric diagnosis , and were urged to treat it in whatever manner and for whatever duration they deemed appropriate ( ie , with " usual care " ) . MAIN OUTCOME MEASURES The treatments that were provided , the patients ' clinical course , and the relationship between the type of treatment and clinical course . RESULTS Health center records indicated that 67 patients ( 73 % ) received a depression-specific treatment in the 8 months following study entry . A majority of the total cohort were prescribed an antidepressant drug . Of the 92 patients , 18 ( 20 % ) were asymptomatic at 8 months ( Hamilton Rating Scale for Depression score , < or = 7 ) . The treatment pattern was not clearly related to the clinical course . CONCLUSIONS The recovery rates for the patients with major depression who were treated with usual care in routine primary care practice s were lower than those anticipated from treatments consistent with the Agency for Health Care Policy and Research guidelines . Further studies of the caregiving elements that influence the effectiveness of depression-specific treatments of patients in primary care setting s are needed |
414 | 28,004,850 | There were no differences in rates of parastomal infection , stomal stenosis or necrosis .
Mesh type and position , and study quality did not have an independent effect on this relationship .
CONCLUSION Mesh placed prophylactically at the time of stoma creation reduced the rate of parastomal hernia , without an increase in mesh-related complications | BACKGROUND Rates of parastomal hernia following stoma formation remain high .
Previous systematic review s suggested that prophylactic mesh reduces the rate of parastomal hernia ; however , a larger trial has recently called this into question .
The aim was to determine whether mesh placed at the time of primary stoma creation prevents parastomal hernia . | Objective : The aim of this study was to assess the reduction in the incidence of parastomal hernia ( PH ) after placement of prophylactic synthetic mesh using a modified Sugarbaker technique when a permanent end-colostomy is needed . Summary of Background Data : Prevention of PH formation is crucial given the high prevalence of PH and difficulties in the surgical repair of PH . Methods : A r and omized , prospect i ve , double-blind , and controlled trial . Rectal cancer patients undergoing laparoscopic abdominoperineal resection with permanent colostomy were r and omized ( 1 : 1 ) to the mesh and nonmesh arms . In the mesh group , a large-pore lightweight composite mesh was placed in the intraperitoneal/onlay fashion using a modified Sugarbaker technique . PH was detected by computed tomography ( CT ) after a minimum follow-up of 12 months . Analysis was per- protocol . Results : The mesh group included 24 patients and the control group 28 . Preoperative data , surgical time , and postoperative morbidity were similar . The median follow-up was 26 months . After CT examination , 6 of 24 PHs ( 25 % ) were observed in the mesh group compared with 18 of 28 ( 64.3 % ) in the nonmesh group ( odds ratio 0.39 , 95 % confidence interval 0.18–0.82 ; P = 0.005 ) . The Kaplan-Meier curves showed significant differences in favor of the mesh group ( long-rank = 4.21 , P = 0.04 ) . The number needed to treat was 2.5 , which confirmed the effectiveness of the intervention . Conclusions : Placement of a prosthetic mesh by the laparoscopic approach following the modified Sugarbaker technique is safe and effective in the prevention of PH , reducing significantly the incidence of PH Purpose Parastomal hernia ( PSH ) is a common complication after colostomy formation . Recent studies indicate that mesh implantation during formation of a colostomy might prevent a PSH . To determine if placement of a retromuscular mesh at the colostomy site is a feasible , safe and effective procedure in preventing a parastomal hernia , we performed a multicentre r and omized controlled trial in 11 large teaching hospitals and three university centres in The Netherl and s. Methods Augmentation of the abdominal wall with a retromuscular light-weight polypropylene mesh ( Parietene Light ™ , Covidien ) around the trephine was compared with traditional colostomy formation . Patients undergoing elective open formation of a permanent end-colostomy were eligible . 150 patients were r and omized between 2010 and 2012 . Primary endpoint of the PREVENT trial is the incidence of parastomal hernia . Secondary endpoints are morbidity , pain , quality of life , mortality and cost-effectiveness . This article focussed on the early results of the PREVENT trial and , therefore , operation time , postoperative morbidity , pain , and quality of life were measured . Results Outcomes represent results after 3 months of follow-up . A total of 150 patients were r and omized . Mean operation time of the mesh group ( N = 72 ) was significantly longer than in the control group ( N = 78 ) ( 182.6 vs. 156.8 min ; P = 0.018 ) . Four ( 2.7 % ) peristomal infections occurred of which one ( 1.4 % ) in the mesh group . No infection of the mesh occurred . Most of the other infections were infections of the perineal wound , equally distributed over both groups . No statistical differences were discovered in stoma or mesh-related complications , fistula or stricture formation , pain , or quality of life . Conclusions During open and elective formation of an end-colostomy , primary placement of a retromuscular light-weight polypropylene mesh for prevention of a parastomal hernia is a safe and feasible procedure . The PREVENT trial is registered at : http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2018 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 Parastomal hernias ( PH ) are frequent with a high morbidity . Three r and omised controlled trials have shown that prophylactic mesh stoma reinforcement significantly reduces their incidence . Implantation and fixation of mesh can be time-consuming , difficult to perform laparoscopically and does not deal with the excessive stretching of the trephine and the creation of an oversized defect . The Stapled Mesh stomAReinforcement Technique ( SMART ) obviates these technical problems . The aim of this study was to assess the safety and efficacy of a novel surgical technique called SMART in preventing parastomal herniation . MethodS MART uses a purpose design ed circular stapling gun ( Compact ™ , Frankenman International Limited ) of various diameters to create a precise trephine and simultaneously fixes a mesh sub-peritoneally and circumferentially to the trephine . Recruited patients were deemed to be high risk for parastomal herniation and r and omisation in a controlled trial was contraindicated . Incidence of parastomal related symptoms and recurrences were documented at clinic visits and radiological confirmation of recurrences , when available , was used for final analysis . A control group of patients who underwent stoma resiting without mesh reinforcement for parastomal herniation was used for comparative purpose s. Results 22 patients ( 16 F:6 M , mean age 49 ± 16 years , BMI 33.0 ± 7.0 ) underwent SMART ( 18 open , 4 laparoscopic ) . There were no intra-operative or early stoma complications . During a median FU of 21 months ( range 12–24 ) , four patients ( 19 % ) were diagnosed with recurrent parastomal herniation , one of which required re-operation . The parastomal herniation rate ( 73 % ) in the control group ( 6 F:5 M ) was significantly higher ( p = 0.003 ) although patients had similar age ( 59 ± 15 years , p = 0.1 ) and body-mass index ( 29.0 ± 3.0 , p = 0.1 ) . ConclusionS MART is a new and simple technique of precisely creating a reinforced stoma trephine at both open and laparoscopic surgery . It obviates the technical disadvantages of traditional stoma formation . This pilot study , in a selected group of patients at high risk for parastomal herniation , indicates that the procedure is clinical ly safe but r and omised controlled trials are required to determine its efficacy in reducing parastomal herniation in all patients undergoing elective stoma formation Background Hernias around ostomies are a very common complication , exceeding 50 % . Only a few studies deal with the prophylactic use of mesh to prevent parastomal hernia revealing promising results . Patients and methods Twenty-two patients undergoing elective rectal surgery with a permanent colostomy — one with an ileostomy and two needing surgical correction of a preexisting colostomy — were enrolled in a prospect i ve study . A specially design ed mesh made of polyvinylidene fluoride with a central whole and a funnel arising ( Dynamesh IPST ® ) was prophylactically implanted using an intraperitoneal onlay technique . The patients were followed for a median of 11 ( range 2–19 ) months by clinical examination every 3 months . Results No infection or any other adverse effect was observed , and no parastomal hernia or stoma protrusion could be detected clinical ly . Twelve patients had a routine computed tomography after 6 months , which also excluded any hernia formation . Conclusion The prophylactic use of Dynamesh IPST ® is a safe and effective procedure preventing stoma complications such as hernia formation or prolapse , at least in the short run Abstract Objective . There are no data on the frequency of parastomal hernia ( PSH ) after ileal conduit with a prophylactic mesh . The primary objective of this study was to determine the prevalence of PSH . Secondary objectives were to elaborate whether age , gender , body mass index ( BMI ) , previous laparotomy or diabetes influenced the outcome ; and to find any mesh-related complications . Material s and methods . In a single centre during 2003 - 2012 , a large-pore , lightweight mesh was placed in a sublay position in 114 consecutive patients with ileal conduits . Preoperative and postoperative patient data were retrospectively collected and cross-sectional follow-up was conducted . During the predefined clinical examination a PSH was defined as any protrusion in the vicinity of the ostomy with the patient straining in both an erect and a supine position . Results .Fifty-eight patients ( 24 women and 34 men , mean age 69 years ) had follow-up examinations after a mean of 35 months ( median 32 months ) . Bladder cancer was the most common cause for surgery . Eight patients ( 14 % ) had a PSH . Age , gender , BMI , previous laparotomy and diabetes did not affect the outcome . No mesh-related complications occurred among the 114 patients with a prophylactic mesh . Conclusions . The prevalence of PSH after ileal conduit with a prophylactic mesh corresponded to that of colostomies with a prophylactic mesh . A prophylactic mesh did not seem to be associated with complications . The degree to which a prophylactic mesh may reduce the rate of PSH after an ileal conduit should be established in r and omized trials Introduction Parastomal hernias occur frequently after placement of a permanent colostomy . Preliminary reports have shown a beneficial effect of placing a mesh at the primary operation to prevent the formation of a parastomal hernia . We studied the safety and prophylactic effect of placing a newly design ed polypropylene mesh in an onlay position at the primary operation . Methods This was a prospect i ve study that included 25 patients scheduled for elective colorectal surgery . Risk factors for development of parastomal hernia were recorded before surgery . A prepared lasercut polypropylene mesh with six “ arms ” was placed in an onlay position . Immediate and long-term complications were evaluated by an experienced stoma nurse and a surgeon . Abdominal ultrasound was performed at 6 and 12 months follow-up . Parastomal hernia was defined as both clinical and ultrasonographic signs of protrusion in the vicinity of the stoma . Results The median follow-up time was 12 ( range , 2–26 ) months . One patient died eight days after surgery . Of the 24 patients included , none had infections or immediate complications after surgery . Two patients had minor complications necessitating a local revision of one of the mesh arms . No other long-term complication was found . Two patients had signs of parastomal hernia at 6 and 12 months follow-up , respectively . Conclusions Placement of a polypropylene mesh in an onlay position at the primary operation is a safe procedure and probably results in a low risk of parastomal hernia occurrence Parastomal hernia ( PSH ) is the most common complication of an end‐colostomy and about one‐quarter of patients need operative repair , which is often unsuccessful . A r and omized trial was carried out to compare the results of using mesh or no mesh at the time of formation of a colostomy with the clinical identification of PSH as the primary outcome Background : The prevalence of terminal parastomal hernia ( PH ) after colostomy placement may be as high as 50 % . The effect of the PH may range from discomfort to life-threatening complications . Surgical procedures for repairing PH are difficult to perform and present a high-failure rate . Objective : To reduce the incidence of PH by implanting a lightweight mesh in the sublay position . Material and Methods : R and omized , controlled , prospect i ve study . Patients were scheduled for permanent end colostomy surgery to treat cancer of the lower third of the rectum , performed by the same colorectal surgery team . An Ultrapro lightweight mesh was inserted in the sublay position in the study group . Using simple r and omization , the sample size required was estimated to be 27 per group . Patients were followed-up clinical ly and radiologically with abdominal computed tomography by an independent clinician and a radiologist who were all blind to the aims of the study , 1 month and every 6 months after surgery . Results : The groups were homogeneous in terms of their clinical and demographic characteristics . Surgical time and postoperative morbidity were similar in the 2 groups . Mortality was 0 . No mesh intolerance was reported . In the clinical follow-up ( median : 29 months , range : 13–49 ) , 11/27 ( 40.7 % ) hernias were recorded in the control group compared with 4/27 ( 14.8 % ) in the study group ( P = 0.03 ) . Abdominal computed tomography identified 14/27 ( 44.4 % ) hernias in the control group compared with 6/27 ( 22.2 % ) in the study group ( P = 0.08 ) . Conclusions : Parastomal placement of a mesh reduces the appearance of PH . The technique is safe , well-tolerated , and does not increase morbidity rates BACKGROUND : A large proportion of patients with a colostomy or an ileostomy develop parastomal hernias . The placement of a reinforcing material at the stoma site may reduce parastomal hernia incidence . OBJECTIVE : We aim ed to assess the safety and efficacy of stoma reinforcement with sublay placement of non-cross-linked porcine-derived acellular dermal matrix at the time of stoma construction . DESIGN : This is a r and omized , patient- and third-party assessor-blind , controlled trial . SETTING S : This study took place in colorectal/general surgery institutions . INTERVENTIONS : Patients were prospect ively r and omly assigned to undergo st and ard end-stoma construction with or without porcine-derived acellular dermal matrix reinforcement . PATIENTS : Patients undergoing construction of a permanent stoma were eligible . A total of 113 patients ( 59 men , 54 women ; mean age , 60 years ; mean BMI , 25.4 kg/m2 ) participated : 58 controls and 55 with reinforcement . MAIN OUTCOMES MEASURES : The incidence of parastomal hernia , safety , and stoma-related quality of life were assessed . RESULTS : Intraoperative complications and blood loss were similar between groups . Quality -of-life scores were similar through 24 months of follow-up . At 24 months of follow-up , the incidence of parastomal hernias was similar for both groups ( 12.2 % of the porcine-derived acellular dermal matrix group and 13.2 % of controls ) . LIMITATIONS : Study limitations include the inclusion of ileostomy and colostomy patients , open and laparoscopic techniques , and small numbers of patients at follow-up . CONCLUSIONS : Safety and quality -of-life data from this r and omized control trial show similar outcomes in both groups . Prosthetic reinforcement of stomas was safe , but it did not significantly reduce the incidence of parastomal hernia formation . Clinical Trial Registration : Identification no. NCT00771407 The parastomal hernia is a continuing challenge , because of the disappointing results of the different procedures available to repair it . The mesh implantation seems to be the best , but not optimal method with 8 - 22 % recurrence rate and about 15 - 20 % other complications . The PHSL ( Polypropylene hernia system large ; Ethicon inc . Johnson and Johnson , USA ) device proved to be an acceptable solution in correction the medium and large parastomal hernia with low recurrence and complication rate . The device enforces the abdominal wall with double mesh layer connected with a tube . The sigmoid colostomy is lifted trough the tube to the abdominal surface . The device was implanted with preventive intent in 14 cases , without any parastomal hernia formation in the first postoperative year . The preventive PHSL mesh implantation at the Miles operation seems to be an useful method for prevention of parastomal hernias Background Parastomal hernia is a major clinical problem . In a r and omized , clinical trial , a prosthetic mesh in a sublay position at the index operation reduced the rate of parastomal hernia at 12-month follow-up , without any increase in the rate of complications . This study was design ed to evaluate the rate of complications after 5 years . Methods Between January 2001 and April 2003 , 54 patients who had a permanent ostomy were r and omized to a conventional stoma or to a stoma with the addition of a mesh in a sublay position . A large-pore , lightweight mesh with a reduced polypropylene content and a high proportion of absorbable material was used . Results After 5 years , 21 patients with a conventional stoma were alive and parastomal herniation was recorded in 17 patients , of whom repair had been dem and ed in 5 . In 15 patients operated on with the addition of a mesh herniation , that did not require repair , was present in 2 ( P < 0.001 ) . No fistulas or strictures developed . No mesh infection was noted and no mesh was removed during the study period . Conclusions At stoma formation , a prophylactic low-weight mesh in a sublay position is a safe procedure that reduces the rate of parastomal hernia Purpose Parastomal hernia ( PSH ) is a very frequent complication after creation of a permanent colostomy . The aim of this study is to assess the safety and prophylactic effect of intraperitoneal onlay mesh ( IPOM ) reinforcement of the abdominal wall at the time of primary stoma formation to prevent PSH occurrence . Material s and methods This multicentre prospect i ve study concerned 20 patients operated for low rectal carcinoma between 2008 and 2010 . Those patients had an elective and potentially curative abdominoperineal excision associated with IPOM reinforcement of the abdominal wall with a round composite mesh centred on the stoma site and covering the lateralised colon . There were 8 men and 12 women with a median age of 69 years ( range : 44–88 ) and a body mass index of 27 ( range : 21–35 ) . The major outcomes analysed in the study were operative time , complications related to mesh and PSH occurrence . Patients were evaluated 1 month after surgery and then every 6 months with physical examination and computed tomography scan ( CT-scan ) . For PSH , we used the classification of Moreno-Matias . Results Surgery was performed by laparoscopy in 17 patients and by laparotomy in 3 ; 12 had an extraperitoneal colostomy , and 8 had a transperitoneal colostomy . The median size of the mesh was 15 cm ( range : 12–15 ) . The median operative time was 225 min ( range : 175–300 ) , and specific time for mesh placement was 15 min ( range : 12–30 ) . One month after surgery , one patient presented with a mild stoma stenosis that was treated successfully by dilatation . With a median follow-up of 24 months ( range : 6–42 ) , no other complication potentially related to the use of the mesh was recorded and no mesh had to be removed . On clinical examination , one patient ( 1/20 = 5 % ) had a stoma bulge that appeared a few months after surgery , but was not associated with symptoms . CT-scan evaluation confirmed that all the patients with a normal clinical examination had no PSH and revealed that the patient with the stoma bulge had a stoma loop hernia ( type 1a hernia ) . This patient was followed up for 36 months , no clinical or radiological aggravation of the stoma loop hernia was observed , and he remained totally asymptomatic . Conclusions With 95 % of excellent results , IPOM reinforcement at the time of end colostomy formation in selected patients is a very promising procedure . A drawback of this technique is the possibility of developing a stoma loop hernia due to sliding of the exiting colon between the covering mesh and the abdominal wall . However , this risk is low , and no adverse clinical consequence for the patient was noted in our series Background This is a prospect i ve study of prophylactic mesh placement in the preperitoneal space at the time of stoma formation to prevent parastomal hernia . Methods Patients undergoing elective permanent stoma formation and resiting of a stoma were included . Patients with peritoneal contamination were excluded . A 6 × 6-cm polypropylene mesh was placed in the preperitoneal space ( no stitches ) , and a circular hole was made to let the bowel come through with ease and the stoma was constructed . At follow-up , the patients were examined st and ing and lying down for parastomal hernia . In the event of clinical uncertainty , a CT scan was done . Results A total of 42 patients ( 20 women , 22 men , mean age 61 years ) were eligible for the study . The patients were followed up for a mean of 31 months ( range 9–68 months ) . There were 29 end-colostomies and 8 end-ileostomies and 5 stomas resited . Four parastomal hernias were detected during the follow-up period ( 9.52 % ) . One required repair due to an ill-fitting stoma bag and leakage . The other three were asymptomatic . One patient developed stomal necrosis which required a new segment of bowel to be brought out through the same opening and the underlying mesh was left undisturbed . Conclusions The results of the 2-year follow-up in this study ( incidence of parastomal herniation 9.5 % ) along with available evidence in the literature ( incidence 0–8.3 % ) , compared to the results of repair make a strong case for the use of a mesh at the time of initial surgery for the formation of any permanent stoma to prevent parastomal herniation UNLABELLED Parastomal hernias are parietal defects adjacent to the stomasite , after ileostomy and colostomy . Their incidence is variable and they are generally underestimated . METHODS Between 2001 and 2010 at the First Surgical Clinic Iasi , we treated 861 incisional hernias , of which there were 31 parastomal hernias in 26 patients ( 3 % ) , 5 of which were recurrent parastomal hernias . Parastomal hernias have been explored clinical ly , through imaging and intraoperatively . Because our experience and literature review have demonstrated that a mesh repair is a safe procedure in the treatment of parastomal hernia , in 2010 we initiated a prospect i ve r and omized trial on the use of prophylactic polypropylene mesh at the time of stoma formation to reduce the risk of parastomal hernia . We enrolled in the study 20 patients with mesh implanted at the primary operation and 22 patients without mesh . The inclusion criteria were : patients with low rectal cancer , stage II-III , irradiated , obese , with a history of hernias , patients who do physical work . RESULTS Most parastomal hernias were asymptomatic ; only six cases with parastomal hernias required emergency surgical treatment . We performed local tissue repair in 16 cases ( 4 cases with recurrent parastomal hernia , stoma relocation in one case ) , sublay mesh repair in 15 cases ( one case with recurrent parastomal hernia ; stoma relocation in 5 cases ) . Postoperative morbidity registered included 4 wound infections ( one case after mesh repair which required surgical reintervention ) and stoma necrosis in one case with strangulation parastomal hernia with severe postoperative evolution and death . After local tissue repair recurrences were seen in 6 cases , after mesh repair we registered recurrence only in one case and no relapse after the relocation of the stoma . The patients with prophylactic mesh at the time of stoma formation to reduce the risk of parastomal hernia were followed for a median of 20 months(range 12 to 28 months ) by clinical examination and ultrasound exam every 3 months . We registered 6 recurrences(27,2 % ) , all in the no mesh cohort . We have not seen any morbidity in patients from the mesh group . CONCLUSIONS Parastomal hernia is a relatively rare disease compared to the number of incisional hernias . With increasing life expectancy st and s we noted increased incidence of parastomal hernia as well . Prophylactic use of mesh during the primary operation is a safe procedure and reduces the risk of parastomal hernia BACKGROUND : Prophylactic placement of a mesh has been suggested to prevent parastomal hernia , but evidence to support this approach is scarce . OBJECTIVE : The aim of this study was to evaluate whether laparoscopic placement of a prophylactic , dual-component , intraperitoneal onlay mesh around a colostomy is safe and prevents parastomal hernia formation after laparoscopic abdominoperineal resection . DESIGN : This is a prospect i ve , multicenter , r and omized controlled clinical trial . SETTING S : This study was conducted at 2 university and 3 central Finnish hospitals . PATIENTS : From 2010 to 2013 , 83 patients undergoing laparoscopic abdominoperineal resection for rectal cancer were recruited . After withdrawals and exclusions , the outcome of 70 patients , 35 patients in each study group , could be examined . INTERVENTIONS : In the intervention group , an end colostomy was created with placement of a intraperitoneal , dual-component onlay mesh and compared with a group with a traditional stoma . MAIN OUTCOME MEASURES : The main outcome measures were the incidence of clinical ly and radiologically detected parastomal hernias and their extent 12 months after surgery . Stoma-related morbidity and the need for surgical repair of parastomal hernia were secondary outcome measures . RESULTS : Parastomal hernia was observed by clinical inspection in 5 intervention patients ( 14.3 % ) and in 12 control patients ( 32.3 % ; p = 0.049 ) . Surgical repair of parastomal hernia was performed in 1 control patient ( 3.2 % ) and in none of the patients in the intervention group . CT detected parastomal hernia in 18 intervention patients ( 51.4 % ) and in 17 control patients ( 53.1 % ; p = 1.00 ) . The extent of hernias was similar according to European Hernia Society classification ( p = 0.41 ) . Colostomy-related morbidity ( 32.3 % vs 14.3 % ; p = 0.140 ) did not differ between the study groups . LIMITATIONS : The study was limited by its small size and short follow-up time . CONCLUSIONS : Prophylactic laparoscopic placement of intraperitoneal onlay mesh does not significantly reduce the overall risk of radiologically detected parastomal hernia after laparoscopic abdominoperineal resection . However , prophylactic mesh repair was associated with significantly lower risk of clinical ly detected parastomal hernia |
415 | 22,695,532 | No statistically significant results were identified by different comparison models or different cut-off point definitions .
No publication bias was observed in continuous and dichotomous data analysis .
In summary , the current systematic review and meta- analysis found that the AR CAG microsatellite repeat polymorphism is unlikely to be a major determining factor in the development of PCOS | A number of studies focusing on the association between the exon 1 CAG repeat polymorphism of the and rogen receptor ( AR ) gene and polycystic ovary syndrome ( PCOS ) have revealed conflicting results .
The current systematic review and meta- analysis was conducted to quantify the strength of the association and to explore potential sources of heterogeneity that may have influenced the results . | The present study was carried out to assess the role of and rogen receptor CAG repeat polymorphism and X chromosome inactivation ( XCI ) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS . CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women . 250 PCOS women and 299 controls were included for this study . And rogen receptor CAG repeat sizes , XCI percentages , and clinical and biochemical parameters were measured . The mean CAG repeat number is similar between the cases ( 18.74±0.13 ) and controls ( 18.73±0.12 ) . The obese PCOS women were significantly more frequent in the < 18 and > 20 CAG repeat category than the lean PCOS women , yielding a highly significant odds ( p = 0.001 ) . Among the women with non-r and om X-inactivation , alleles with < 19 repeats were more frequently activated among cases than controls ( p = 0.33 ) . CAG repeat polymorphism by itself can not be considered as a useful marker for discriminating PCOS . We observed a trend of preferential activation of the shorter allele among the PCOS cases with non r and om XCI pattern . In the obese PCOS women , this microsatellite variation may account for the hyper and rogenicity to a larger extent than the lean PCOS women Methods of sample size and power calculations are review ed for the most common study design s. The sample size and power equations for these design s are shown to be special cases of two generic formulae for sample size and power calculations . A computer program is available that can be used for studies with dichotomous , continuous , or survival response measures . The alternative hypotheses of interest may be specified either in terms of differing response rates , means , or survival times , or in terms of relative risks or odds ratios . Studies with dichotomous or continuous outcomes may involve either a matched or independent study design . The program can determine the sample size needed to detect a specified alternative hypothesis with the required power , the power with which a specific alternative hypothesis can be detected with a given sample size , or the specific alternative hypotheses that can be detected with a given power and sample size . The program can generate help messages on request that facilitate the use of this software . It writes a log file of all calculated estimates and can produce an output file for plotting power curves . It is written in FORTRAN-77 and is in the public domain Hyper and rogenism is currently thought to be central to the pathogenesis of polycystic ovarian syndrome ( PCOS ) , a common endocrine disorder in premenopausal women characterized by irregular menstruation and anovulatory infertility . Although hyper and rogenism is characteristic , some women with PCOS have normal serum and rogen levels . All and rogens act through the X-linked and rogen receptor ( AR ) , the N-terminal domain of which contains a polyglutamine tract encoded by a highly polymorphic CAG trinucleotide repeat tract . Recently , variations in this CAG microsatellite tract , while remaining within the normal polymorphic range ( 11 - 38 CAGs ) , have been inversely correlated with receptor activity . Thus , short tracts are associated with high intrinsic AR activity and increased severity and earlier age of onset of the and rogen-regulated tumor prostate cancer , whereas longer CAG tracts are associated with low AR activity and oligospermic infertility . To investigate the role of the CAG repeat tract in PCOS , we measured its length in 91 patients with ultrasound diagnosis of polycystic ovaries , irregular menstrual cycles , and anovulatory infertility and compared them to 112 control subjects of proven fertility with regular menses . Fluorescent-labeled DNA fragments containing the CAG repeat tract were amplified from leucocytic DNA , and their lengths were compared with internal size markers on an automated DNA Sequencer . There were no differences in the mean CAG length between patients and controls when both alleles were considered together or separately . Because there is a subset of PCOS patients whose serum and rogens are normal , we compared differences in CAG length between patients whose serum testosterone ( T ) levels were below the normal laboratory mean , to those that were higher . There was a trend for a lower mean CAG biallelic length among anovulatory patients with T less than 1.73 nmol/L compared with those whose T was more than 1.73 nmol/L ( 22.47 + /- 0.36 vs. 23.25 + /- 0.29 ) . This difference in CAG length between patients with low and high T levels ( 20.38 + /- 0.51 vs. 21.98 + /- 0.29 ) was highly significant ( P = 0.004 ) when only the shorter allele of each individual was considered . Ethnic differences were also evident in our data ; Indian subjects had a significantly shorter AR-CAG length compared with Chinese , being 22.08 + /- 0.50 and 23.16 + /- 0.17 , respectively . Our data indicate an association between short CAG repeat length and the subset of anovulatory patients with low serum and rogens , suggesting that the pathogenic mechanism of polycystic ovaries in these patients could be due to the increased intrinsic and rogenic activity associated with short AR alleles CONTEXT Genetically determined heightened and rogen sensitivity may influence the phenotype of polycystic ovary syndrome ( PCOS ) . To date , studies of the and rogen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS . OBJECTIVE We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS . We also compared X-chromosome inactivation between cases and controls . DESIGN Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation . Association analyses were performed . SETTING Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham ; controls were recruited from the surrounding community . Genotyping took place at Cedars-Sinai Medical Center in Los Angeles . PARTICIPANTS Participants included 330 women with PCOS and 289 controls ( 77 % white , 23 % black ) . MAIN MEASUREMENTS And rogen receptor genotype , X-chromosome methylation , and phenotyping for PCOS were measured . RESULTS A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS . X-chromosome inactivation was not different comparing cases with controls ; however , in the subset with nonr and om inactivation , the chromosome bearing the shorter CAG allele was preferentially active in PCOS women . CONCLUSIONS Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of and rogen receptors expressed from alleles with fewer CAG repeats , suggesting inherited alteration in and rogen sensitivity may contribute to PCOS . In some women , such heightened sensitivity may also result from preferential expression of and rogen receptors with shorter alleles . Thus , genetic and epigenetic changes may be involved in the pathogenesis of PCOS 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 We studied the effects of the SHBG (TAAAA)(n ) and and rogen receptor gene [ AR ] (CAG)(n ) allele length on endocrine-metabolic features and body composition ( by dual-energy X-ray absorptiometry ) before and after 1 year on metformin ( 850 mg/d ) in 70 girls with polycystic ovary syndrome after precocious pubarche ; allele lengths were assessed by polymerase chain reaction in both patients and in population control subjects ( n = 107 ) . Longer SHBG (TAAAA)(n ) alleles ( > 8 repeats ) were associated with more improvement of the lipid profile after 1 year on metformin , whereas longer AR (CAG)(n ) alleles were related to more normalization of the and rogen and lipid levels after therapy ; longer alleles in both genes had an additive effect on the beneficial changes of SHBG , T , and lipids after metformin |
416 | 25,308,577 | Although there is a wide variability in selected population , dose regimen and final outcomes , nutritional supplements both alone and in combination seems to be able to improve semen parameters ( sperm count , sperm motility and morphology ) and pregnancy rate in infertile men .
CONCLUSIONS There are rising evidence s from published r and omized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT .
This improvement , however , is not consistent and there is a wide variation in the treatment regimens used . | OBJECTIVE Infertility affects 15 % of couples in fertile age .
Male factor is a cause of infertility in almost half of cases , mainly due to oligoasthenoteratozoospermia ( OAT ) .
The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility . | PURPOSE We investigated the effects of the administration of ubiquinol ( a reduced form of coenzyme Q(10 ) ) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia . MATERIAL S AND METHODS A total of 228 men with unexplained infertility were r and omly assigned 1:1 into 2 groups . Group 1 ( 114 ) received 200 mg ubiquinol daily by mouth for 26 weeks and group 2 ( 114 ) received a similar regimen of placebo . After completion of the 26-week treatment phase , all participants were followed for another 12-week off-drug period . Primary outcomes were improvement in sperm density , sperm motility and sperm strict morphology . RESULTS At the end of the 26-week treatment period mean ± SD sperm density in the ubiquinol and placebo groups was 28.7 ± 4.6 × 10(6)/ml and 16.8 ± 4.4 × 10(6)/ml ( p = 0.005 ) , sperm motility was 35.8 % ± 2.7 % and 25.4 % ± 2.1 % ( p = 0.008 ) , and sperm strict morphology was 17.6 % ± 4.4 % and 14.8 % ± 4.1 % ( p = 0.01 ) of normal sperm , respectively . During the treatment period serum follicle-stimulating hormone levels decreased significantly ( p = 0.02 ) and serum inhibin B concentrations increased significantly ( p = 0.01 ) . During the off-drug period semen parameters gradually returned to baseline values but the differences were still significant for sperm density ( p = 0.03 ) and sperm motility ( p = 0.03 ) . The correlation coefficients analysis revealed a positive association between the duration of treatment with ubiquinol and sperm density ( r = 0.74 , p = 0.017 ) , sperm motility ( r = 0.66 , p = 0.024 ) and sperm morphology ( r = 0.57 , p = 0.027 ) . CONCLUSIONS Ubiquinol was significantly effective in men with unexplained oligoasthenoteratozoospermia for improving sperm density , sperm motility and sperm morphology OBJECTIVE To determine the effectiveness of the in vivo administration of vitamin E as treatment for reactive oxygen species-associated male infertility . SETTING University-based center for reproductive medicine . DESIGN Double-blind r and omized placebo cross-over controlled trial . PATIENTS , PARTICIPANTS Thirty healthy men with high levels of reactive oxygen species generation in semen and a normal female partner . INTERVENTIONS Patients were allocated to two groups according to the blinded r and omization . Each patient received either 600 mg/d of vitamin E ( Ephynal , 300 mg tablets ; F. Hoffman-La Roche Ltd. , Basle , Switzerl and ) ( order A ) or identical placebo tablets ( order B ) for 3 months . Then after a 1-month wash-out period the patients were crossed-over to the other treatment . MAIN OUTCOME MEASURES Improvement in the in vitro function of the spermatozoa measured by conventional semen analysis , computerized motility assessment , determination of reactive oxygen species generation , binding to the zona pellucida of the unfertilized human oocyte in a competitive zona binding assay , development of hyperactivated motility ( both spontaneous and in the presence of 20 % of the natural agonist , human follicular fluid ) and pregnancy . RESULTS Rise in the blood serum vitamin E levels after treatment accompanied by improvement in one of the sperm function tests : the zona binding assay . The zona binding ratio for order A improved from 0.2 ( range 0 to 0.5 ) before treatment to 0.5 ( range 0.1 to 1.0 ) after treatment , the corresponding values for order B were 0.2 ( range 0 to 1.0 ) before treatment and 0.3 ( range 0.1 to 0.7 ) after treatment . CONCLUSION Oral administration of vitamin E significantly improves the in vitro function of human spermatozoa as assessed by the zona binding test OBJECTIVE To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers . DESIGN Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d . SETTING Department of Obstetrics and Gynecology , The University of Texas Medical Branch . PARTICIPANTS Seventy-five men ( 20 to 35 years old ) r and omly divided into one of three supplementation groups : placebo , 200 mg and 1,000 mg of ascorbic acid . MAIN OUTCOME Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups . RESULTS The placebo group showed no improvement in sperm quality . The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group . Pearson 's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities . CONCLUSIONS Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality We recently introduced reduced glutathione into the therapeutic protocol s in some selected cases of dyspermia . This therapy improved semen quality both in a pilot follow-up study and in a double-blind cross-over trial . This improvement was seen in patients with varicocele and germ-free genital tract inflammation , two pathologies in which production of reactive oxygen species or other toxic compounds could have a pathogenic role . Polyunsaturated fatty acids of phospholipids play a major role in membrane constitution and function and are one of the main targets of the lipoperoxidative process . Therefore , to underst and the therapeutic action of reduced glutathione , we selected infertile patients and studied the modifications produced by the therapy in seminal parameters , biochemical sperm membrane parameters , and the pattern of fatty acids of phospholipids from blood serum and red blood cell membranes ( a model widely accepted as representative of general cell membrane status ) . The results showed an improvement in both sperm parameters and cell membrane characteristics . This study suggests that biochemical modifications in membrane constitution could explain the seminal results of glutathione therapy . On the other h and , it seems likely that only subjects with systemic membrane disturbances associated with and rological pathologies express this membrane damage in spermatozoa , result ing in dyspermia . This sperm alteration can be partially reversed by glutathione therapy if the structural cell membrane damage is not too severe AIM OF THE STUDY To evaluate with an open-label study the efficacy and safety of a complex of nutritional supplements with antioxidant activity ( L-carnitine , acetyl-L-carnitine , fructose , citric acid , selenium , coenzyme Q10 , zinc , ascorbic acid , cyanocobalamin , folic acid ) in primary infertile patients with idiopathic astenoteratozoospermia . METHODS The study was conducted in a population of 114 infertile men ( 96 completed the study ) diagnosed with idiopathic astenoteratozoospermia since at least 18 months . Patients orally received a formulation ( Proxeed - Sigma-Tau ) containing L-carnitine 145 mg , acetyl-L-carnitine 64 mg , fructose 250 mg , citric acid 50 mg , selenium 50 mcg , coenzyme Q10 20 mg , zinc 10 mg , ascorbic acid 90 mg , cyanocobalamin 1.5 mcg , folic acid 200 mcg in combination once a day for 4 months . RESULTS At the end of study , the mean sperm progressive motility showed a statistically significant increase from 18.3 + /- 3.8 to 42.1 + /- 5.5 . Sixteen patients achieved pregnancy during the study . No significant improvement were observed for sperm density and rate of morphologically normal forms . The treatment was well tolerated . CONCLUSIONS Carnitines in association with others functional substances can improve the most important parameters of sperm quality Purpose Surgical repair of varicocele has long been a procedure to correct spermatogenesis . However , the outcome has been reported to be inadequate . We combined varicocelectomy with supplement therapy to evaluate the concurrent effect of these procedures . Methods A prospect i ve r and omized controlled study was undertaken to investigate the effects of zinc sulfate , folic acid and zinc sulfate/folic acid on sperm quality , protamine content and acrosomal integrity following surgical repair of varicocele . Male subjects with palpable varicocele were included in the study and r and omized into four groups . Subjects received Zinc sulfate , Follic acid , Zinc sulfate/Follic acid or placebo for 6 months . A semen sample was obtained before surgery and 3 and 6 months after surgical repair . Semen sample s were evaluated for sperm parameters as well as chromatin content and acrosomal integrity . Results Most of the evaluated parameters showed a mild improvement after varicocelectomy in the placebo group . Interestingly , co-administration of Zinc sulfate and folic acid improved most factors significantly . Folic acid administration but not zinc sulfate could increase sperm number . Hence , Zinc sulfate was better than folic acid when change in morphology was assessed , and none of them was significantly effective in sperm motility . In Zinc sulfate and Follic acid groups , protamine content and halo formation rate significantly improved . Conclusions We may conclude that co-administration of zinc and folic acid significantly improved sperm parameters and increased varicocelectomy outcomes . So , medical treatment with compatible drugs after surgery might be advantageous for obtaining acceptable results The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia ( OAT ) . Idiopathic and varicocele OAT patients were r and omized into 3 groups . Each group was composed of varying degrees of left varicoceles ( grade d into 5 grade s with echo-color Doppler ) and of idiopathic OATs . Group 1 used a placebo , group 2 used oral L-carnitine ( 2 g/d ) + acetyl-L-carnitine ( 1 g/d ) , group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days . Drugs were administered for 6 months . The groups were composed as follows : group 1 , 71 varicoceles and 47 idiopathic OATs ; group 2 , 62 varicoceles and 39 idiopathic OATs ; group 3 , 62 varicoceles and 44 idiopathic OATs . Sperm concentration , motility , and morphology before during and after treatments were assessed . Pregnancy rates and side effects were recorded . Group 1 did not have modified sperm patterns during treatment . Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grade s I , II , and III varicocele , but not in grade s IV and V. Group 3 had significantly increased sperm parameters in all patients , with the exception of grade V varicocele . Group 3 sperm patterns proved significantly higher during therapy than group 2 . All sperm patterns fell to baseline after therapy suspension . Minor side effects occurred . Pregnancy rates were 1.7 % ( group 1 ) , 21.8 % ( group 2 ) , and 38.0 % ( group 3 ) ( P < .01 ) . L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low- grade varicoceles and idiopathic OATs Sperm DNA fragmentation is known to compromise male fertility . Previous findings have suggested the implication of oxidative stress in the etiology of this pathological condition . The present study was conducted to find out if the pathologically increased incidence of DNA fragmentation in ejaculated spermatozoa can be reduced by oral treatment with two antioxidants , vitamins C and E. Sixty-four men with unexplained infertility and an elevated ( > or = 15 % ) percentage of DNA-fragmented spermatozoa in the ejaculate were r and omized between an antioxidant treatment ( 1 g vitamin C and 1 g vitamin E daily for 2 months ) group and a placebo group . Sperm DNA fragmentation was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay before and after treatment . No differences in basic sperm parameters were found between the antioxidant treatment and the placebo group before or after treatment . However , the percentage of DNA-fragmented spermatozoa was markedly reduced ( P < .001 ) in the antioxidant treatment group after the treatment ( 9.1 + /- 7.2 ) as compared with the pretreatment values ( 22.1 + /- 7.7 ) . No difference in the pretreatment and posttreatment incidence of sperm DNA fragmentation was observed in the placebo group . These data show that sperm DNA damage can be efficiently treated with oral antioxidants administered during a relatively short time period Peroxidative damage induced by reactive oxygen species ( ROS ) has been proposed as one of the major causes of defective sperm function . The ROS detected in semen reflect an imbalance between ROS generation and degradation . The objective of the present study was to investigate the relationship between the oxidative and anti-oxidative potential in semen of infertile patients and healthy donors . Specimens were obtained from 28 patients and 18 healthy donors ( controls ) . A conventional spermiogram , measurement of luminol-chemiluminescence ( CL ) in washed semen , and high performance liquid chromatography determination of ascorbic acid and urate concentrations in seminal plasma were performed . Oligozoospermic patients exhibited higher CL signals than controls ( P < 0.001 ) . Normozoospermic patients showed lower ascorbic acid ( mean + /- SE : 491 + /- 46 microM , P < 0.04 ) and urate concentrations ( 320 + /- 22 microM , P < 0.009 ) than controls ( 612 + /- 35 and 426 + /- 26 microM respectively ) . Seminal plasma ascorbic acid was negatively correlated with the CL signals ( P < 0.0006 ) and positively correlated with the percentage of spermatozoa with normal morphology ( P < 0.006 ) . This is the first report of a correlation between the anti-oxidant ascorbic acid in seminal plasma and ROS generation in human semen . Furthermore , the reduced ascorbic acid/urate concentrations found in semen of normozoospermic patients might be indicative of a reduced anti-oxidative protection OBJECTIVES To determine whether the decline in selenium intake and selenium status in men in the West of Scotl and might be a contributory factor to male subfertility . PATIENTS AND METHODS Two semen sample s were collected from patients attending a subfertility clinic and those patients with sample s showing reduced motility were invited to participate in an ethically approved double-blind clinical ly controlled trial with informed consent . Sixty-nine patients were recruited and received either placebo , selenium alone or selenium plus vitamins A , C and E daily for 3 months . A further semen sample was collected at the end of the trial . Plasma selenium status was determined at the beginning and end of the trial period , as was total sperm density and motility . RESULTS Plasma selenium concentrations were significantly ( P < 0.001 ) higher in both selenium-treated groups than in controls . No significant effect of treatment on sperm density was recorded . Sperm motility increased in both selenium-treated groups , in contrast to a slight decline in the placebo group , but the difference was not significant . However , as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment . On this basis , selenium treatment significantly ( P < 0.002 ) increased plasma selenium concentrations and sperm motility ( P = 0.023 ) but sperm density was again unaffected . Five men ( 11 % ) achieved paternity in the treatment group , in contrast to none in the placebo group . CONCLUSION This trial confirms the result of an earlier study , that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception . However , not all patients responded ; 56 % showed a positive response to treatment . The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet PURPOSE We explored the efficacy of selenium and /or or N-acetyl-cysteine for improving semen parameters in infertile men , and the associations among semen quality and the concentrations of selenium and N-acetyl-cysteine in seminal plasma . MATERIAL S AND METHODS The study included 468 infertile men with idiopathic oligo-asthenoteratospermia who were r and omized to receive 200 microg selenium orally daily ( selenium group of 116 ) , 600 mg N-acetyl-cysteine orally daily ( N-acetyl-cysteine group of 118 ) , 200 microg selenium plus 600 mg N-acetyl-cysteine orally daily ( selenium plus N-acetyl-cysteine group of 116 ) or similar regimen of placebo ( control group of 118 ) for 26 weeks , followed by a 30-week treatment-free period . These patients provided blood sample s for the measurement of serum testosterone , estradiol , follicle-stimulating hormone , luteinizing hormone , prolactin , inhibin B , selenium and N-acetyl-cysteine . Semen sample s were also obtained for routine semen analysis , and the measurement of seminal plasma selenium and N-acetyl-cysteine . RESULTS In response to selenium and N-acetyl-cysteine treatment serum follicle-stimulating hormone decreased but serum testosterone and inhibin B increased . All semen parameters significantly improved with selenium and N-acetyl-cysteine treatment . Administering selenium plus N-acetyl-cysteine result ed in additive beneficial effects . A significant positive correlation existed between the seminal plasma concentrations of selenium and N-acetyl-cysteine , and semen parameters . A strong correlation was observed between the sum of the selenium and N-acetyl-cysteine concentrations , and mean sperm concentration ( r = 0.67 , p = 0.01 ) , sperm motility ( r = 0.64 , p = 0.01 ) and percent normal morphology ( r = 0.66 , p = 0.01 ) . CONCLUSIONS These results indicate that supplemental selenium and N-acetyl-cysteine improve semen quality . We advocate their use for male infertility treatment OBJECTIVE To evaluate whether the association of antioxidants and anti-inflammatory compounds may be beneficial in treatment of patients with abacterial prostatovesiculoepididymitis ( PVE ) and elevated seminal leukocyte concentrations . DESIGN Open , prospect i ve , r and om study . SETTING Academic research environment . PATIENT(S ) Ninety-eight patients with PVE who had increased seminal leukocyte concentrations ( > 1 x 10(6 ) cells/mL ) . Carnitines ( group A ; n = 30 ) or nonsteroidal anti-inflammatory drugs ( group B ; n = 16 ) for 4 months ; nonsteroidal anti-inflammatory drugs for 2 months , followed by treatment with carnitines for 2 months ( group C ; n = 26 ) ; or nonsteroidal anti-inflammatory treatment given concomitantly with carnitines ( group D ; n = 26 ) for 4 months . MAIN OUTCOME MEASURE(S ) Semen variables , production of reactive oxygen species , and pregnancy outcome were evaluated before and after treatment and following a 3-month washout period . RESULT ( S ) Patients in group C had the highest reduction in production of reactive oxygen species associated with increased sperm motility and viability . Groups B and D experienced intermediate effects , and group A experienced the least effect . CONCLUSION ( S ) Antioxidant treatment with carnitines is effective in patients with abacterial PVE and increased seminal leukocyte concentrations if these patients have been pretreated with nonsteroidal anti-inflammatory drugs Numerous studies have reported beneficial effects of antioxidant drugs on semen quality , but there is no well-defined therapeutical protocol in male infertility . This study aim ed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters . The study included 54 voluntary and infertile men who produced semen sample s for spermiogram and for spectrophotometric measurement of a lipid peroxidatio n marker , the malondialdehyde ( MDA ) , and produced blood sample s for high-perf ormance liquid chromatography assessment of serum vitamin E level . The trial was r and omized and open . Twenty-eight men were supplemented daily by vitamin E ( 400 mg ) and selenium ( 225 µg ) , during 3 months . The remaining 26 patients received vitamin B ( 4,5 g/day ) for the same duration . Only 20 patients achieved their treatment and returned for control analysis . MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels . In contrast to vitamin B supplementation , vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility . The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment Asthenospermia is the main factor of male infertility among patients consulting the Asir Infertility Center in Abha , Saudi Arabia . Lipid peroxidation occurring in both the seminal plasma and spermatozoa was estimated by malondialdehyde ( MDA ) concentration . Spermatozoal MDA concentration was higher in men with decreased sperm motility . The MDA concentration in the seminal plasma exhibited no relationship with sperm concentration , sperm motility , the number of immotile spermatozoa , or even the absence of spermatozoa . The MDA concentration in sperm pellet suspensions of asthenospermic and oligoasthenospermic patients was almost twice that of the normospermic males . The MDA concentration in the sperm pellet suspension from normospermic or oligospermic patients was about 10 % that in the seminal plasma . However , the MDA concentration in the sperm pellet suspension of asthenospermic or oligoasthenospermic patients was about 15 % that in the seminal plasma . Treatment of asthenospermic patients with oral Vitamin E significantly decreased the MDA concentration in spermatozoa and improved sperm motility . Eleven out of the 52 treated patients ( 21 % ) impregnated their spouses ; nine of the spouses successfully ended with normal term deliveries , whereas the other two aborted in the first trimester . No pregnancies were reported in the spouses of the placebo-treated patients The aim of this study was to follow up whether the modification of pro-antioxidant status by oral thiol administration such as N-acetylcysteine and alpha-lipoic acid affects the hematological response . Twenty-eight healthy men participated in two independent experiments . Subjects were r and omly assigned to one of four groups : controls ( C(NAC ) and C(ALA ) ) , N-acetylcysteine ( NAC ) and alpha-lipoic acid ( ALA ) . 1200 mg of N-acetylcysteine , 600 mg of alpha-lipoic acid or placebo were administered for 8 days in two doses . NAC or ALA administration significantly elevated plasma total antioxidant status ( TAS ) and reduced protein carbonylation ( PC ) and lipid peroxidation ( TBARS ) by more than 30 % . The reduced glutathione ( GSH ) and hematological parameters changed only in response to NAC administration . NAC significantly elevated the level of GSH ( + 33 % ) , EPO ( + 26 % ) , Hb ( + 9 % ) and Hct ( + 9 % ) compared with C(NAC ) . The mean corpuscular volume ( MCV ) and the mean corpuscular hemoglobin ( MCH ) also increased by more than 12 % after NAC . The numerous negative or positive correlations between the measures of TAS , PC , TBARS and hematological parameters were found , which suggest the NAC-induced interaction between pro-antioxidant and hematological values . Our study has shown that both N-acetylcysteine and alpha-lipoic acid intake reveal an antioxidant action , but only N-acetylcysteine improves the haematological response We investigated the effects of folic acid and zinc sulphate supplementation on the improvement of sperm function in subfertile oligoasthenoteratozoospermic ( OAT ) men . Eighty‐three OAT men participated in a 16‐week intervention r and omised , double‐blind clinical trial with daily treatment of folic acid ( 5 mg day−1 ) and zinc sulphate ( 220 mg day−1 ) , or placebo . Before and after treatment , semen and blood sample s were obtained for determining sperm concentration , motility , and morphology , sperm viability , sperm mitochondrial function , sperm chromatin status using toluidine blue , aniline blue , acridine orange and chromomycin A3 staining ; and semen and blood folate , zinc , B12 , total antioxidant capacity ( TAC ) and malondialdehyde ( MDA ) concentrations . Sperm concentration ( ×106 ml−1 ) increased in subfertile men receiving the combined treatment of folic acid and zinc sulphate and also in the group receiving only folic acid treatment ; however , it was not statistically significant ( P = 0.056 and P = 0.05 , respectively ) . Sperm chromatin integrity ( % ) increased significantly in subfertile men receiving only zinc sulphate treatment ( P = 0.048 ) . However , this improvement in sperm quality was not significant after adjusting placebo effect . This study showed that zinc sulphate and folic acid supplementation did not ameliorate sperm quality in infertile men with severely compromised sperm parameters , OAT . Male infertility is a multifactorial disorder , and also nutritional factors play an important role in results of administration of supplementation on sperm parameters . However , these results should be confirmed by multiple studies in larger population s of OAT men 64 infertile men with oligozoospermia took part in a double blind cross-over trial . Each patient received matching capsules of a placebo and arginine for periods of 12 weeks . There was no difference in the conception rates of the wives or changes in the quality of the semen during each period of treatment OBJECTIVE To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia . DESIGN Placebo-controlled double-blind r and omized trial . SETTING University tertiary referral center . PATIENT(S ) Sixty infertile patients ( aged 20 - 40 years ) with the following baseline sperm selection criteria : concentration , 10 to 40 x 10(6)/mL ; forward motility , < 15 % ; total motility , 10 % to 40 % ; and atypical forms , < 80 % . Fifty-six patients completed the study . INTERVENTION(S ) Patients were su bmi tted to a combined treatment of l-carnitine ( 2 g/d ) and l-acetyl-carnitine ( 1 g/d ) or of placebo ; the study design was 2 months ' wash-out , 6 months of therapy or of placebo , and 2 months ' follow-up . MAIN OUTCOME MEASURE(S ) Variation in the semen parameters that were used for patient selection . RESULT ( S ) Even though increases were seen in all sperm parameters after combined carnitine treatment , the most significant improvement in sperm motility ( both forward and total ) was present in patients who had lower initial absolute values of motile sperm ( < 4 x 10(6 ) forward or < 5 x 10(6 ) total motile spermatozoa per ejaculate ) . CONCLUSION ( S ) Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility , especially in groups with lower baseline levels Glutathione therapy was used for 2 months in a placebo-controlled double-blind cross-over trial of 20 infertile patients with dyspermia associated with unilateral varicocele ( VAR ) or germ-free genital tract inflammation ( INF ) . The patients received either glutathione ( group 1 ) or placebo ( group 2 ) for 2 months , then they crossed over to the alternative treatment for a further 2 months . The patients were r and omly and blindly assigned to treatment ( one i.m . injection every other day of either 600 mg glutathione or an equal volume of a placebo preparation ) . The st and ard semen analysis and the computer-assisted sperm motility analyses were carried out before treatment and during the trial . Statistical cross-over analysis , case-control study and treatment efficacy test were carried out on groups 1 and 2 and differences in the effects of therapy between VAR and INF patients with varicocele or inflammation were tested . Glutathione therapy demonstrated a statistically significant positive effect on sperm motility , in particular on the percentage of forward motility , the kinetic parameters of the computerized analysis and on sperm morphology . The findings of this study indicate that glutathione therapy could represent a possible therapeutical tool for both of the selected and rological pathologies On the basis of reported experimental and clinical studies we investigated the effectiveness of L-carnitine administration in a group of patients with idiopathic asthenospermia . A favourable effect of the compound on sperm motility and rapid linear progression has been shown in 37 out of 47 patients treated . In addition , the total number of sperms increased . L-carnitine was supplemented orally by a daily dosage of 3 g for three months OBJECTIVE To evaluate the effectiveness of coenzyme Q(10 ) treatment in improving semen quality in men with idiopathic infertility . DESIGN Placebo-controlled , double-blind r and omized trial . SETTING And rology Unit , Department of Internal Medicine , Polytechnic University of Marche , Italy . PATIENT(S ) Sixty infertile patients ( 27 - 39 years of age ) with the following baseline sperm selection criteria : concentration > 20 x 10(6)/mL , sperm forward motility < 50 % , and normal sperm morphology > 30 % ; 55 patients completed the study . INTERVENTION(S ) Patients underwent double-blind therapy with coenzyme Q(10 ) , 200 mg/day , or placebo ; the study design was 1 month of run-in , 6 months of therapy or placebo , and 3 months of follow-up . MAIN OUTCOME MEASURE(S ) Variations in semen parameters used for patient selection and variations of coenzyme Q(10 ) and ubiquinol concentrations in seminal plasma and spermatozoa . RESULT ( S ) Coenzyme Q(10 ) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment , as well as spermatozoa motility . A weak linear dependence among the relative variations , baseline and after treatment , of seminal plasma or intracellular coenzyme Q(10 ) and ubiquinol levels and kinetic parameters was found in the treated group . Patients with a lower baseline value of motility and levels of coenzyme Q(10 ) had a statistically significant higher probability to be responders to the treatment . CONCLUSION ( S ) The exogenous administration of coenzyme Q(10 ) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia PURPOSE We determined the efficacy of coenzyme Q10 supplementation on semen parameters , sperm function and reproductive hormone profiles in infertile men . MATERIAL S AND METHODS A total of 212 infertile men with idiopathic oligoasthenoteratospermia were r and omly assigned to receive 300 mg coenzyme Q10 ( Kaneka , Osaka , Japan ) orally daily ( 106 in group 1 ) or a similar placebo regimen ( 106 in group 2 ) during a 26-week period , followed by a 30-week treatment-free phase . Two semen analyses , acrosome reaction test , immunobead test for antisperm antibody , and determination of resting levels of luteinizing hormone , follicle-stimulating hormone , prolactin , testosterone and inhibin B were done in all participants . Blood and seminal plasma total coenzyme Q10 was also assessed . RESULTS Significant improvement in sperm density and motility was evident with coenzyme Q10 therapy ( each p = 0.01 ) . Using the Kruger classification sperm morphology evaluation revealed an increase in the percent of normal forms in the coenzyme Q10 group ( p = 0.07 ) . A positive correlation was found between treatment duration with coenzyme Q10 and sperm count ( r = 0.46 , p = 0.03 ) as well as with sperm motility ( r = 0.45 , p = 0.04 ) and sperm morphology ( r = 0.34 , p = 0.04 ) . The coenzyme Q10 group had a significant decrease in serum follicle-stimulating hormone and luteinizing hormone at the 26-week treatment phase ( each p = 0.03 ) . By the end of the treatment phase the mean + /- SD acrosome reaction had increased from 14 % + /- 8 % and 15 % + /- 8 % to 31 % + /- 11 % and 16 % + /- 10 % in the coenzyme Q10 and placebo groups , respectively ( p = 0.01 ) . CONCLUSIONS Coenzyme Q10 supplementation result ed in a statistically significant improvement in certain semen parameters . However , further studies are needed to draw a final conclusion and evaluate the effect of coenzyme Q10 supplementation on the pregnancy rate Summary . The aim of the study described here was to evaluate any possible effect of L‐carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres . One hundred patients received 3 g d−1 of oral L‐carnitine for 4 months . Sperm parameters were studied before , during and after this treatment . Motility was also studied by means of a computer‐assisted sperm analysis OBJECTIVE To evaluate the effectiveness of L-carnitine ( LC ) or L-acetyl-carnitine ( LAC ) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen . DESIGN Placebo-controlled , double-blind , r and omized trial . SETTING And rology unit , Department of Internal Medicine , Polytechnic University of Marche , Italy . PATIENT(S ) Sixty infertile men , ages 20 to 40 years , with the following baseline sperm selection criteria : concentration > 20 x 10(6)/mL , sperm forward motility < 50 % , and normal sperm morphology > 30 % ; 59 patients completed the study . INTERVENTION(S ) Patients underwent a double-blind therapy of LC 3 g/d , LAC 3 g/d , a combination of LC 2 g/d and LAC 1 g/d , or placebo . The study design was 1 month of run in , 6 months of therapy or placebo , and 3 months of follow-up evaluation . MAIN OUTCOME MEASURE(S ) Variations in semen parameters used for patient selection , and variations in total oxyradical scavenging capacity of the seminal fluid . RESULT ( S ) Sperm cell motility ( total and forward , including kinetic features determined by computer-assisted sperm analysis ) increased in patients to whom LAC was administered both alone or in combination with LC ; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months . The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features . Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment . CONCLUSION ( S ) The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population Abstract Background and objective : L-carnitine is an essential molecule involved in mitochondrial metabolism , controlling the transport of acetyl and acyl groups across the mitochondrial inner membrane . Carnitine and acetylated carnitine ( L-acetylcarnitine ) are found in high concentrations in the epididymis , where they also act as antioxidants , protecting spermatozoa against damage caused by reactive oxygen species . In this open study we investigated the correlation between seminal carnitine levels and spermatozoal function , and the effect of combined L-carnitine + L-acetylcarnitine therapy , in infertile men . Patients and methods : 170 infertile men were enrolled in this study . Patients were divided into those with a total sperm motility below the normal WHO range ( < 50 % motility , group 1 [ n = 102 ] ) and those with total sperm motility within the normal range ( > = 50 % motility , group 2 [ n = 68 ] ) . Patients in group 1 were further divided into two groups : those with primary or secondary azoospermia ( 1B [ n = 36 ] ) , and those without ( 1A [ n = 66 ] ) . Patients in group 1A received L-carnitine 1 g/day and L-acetylcarnitine 500 mg twice daily for 6 months . Seminal carnitine levels were measured and correlated with sperm count and motility , eosin test , hypo-osmotic swelling test , acridine orange test for sperm nuclear DNA integrity and sperm kinetics evaluated by computer-assisted sperm analysis in all patients . Results : There was a significant correlation between seminal carnitine concentration and sperm concentration , total sperm count , sperm total motility , rapid forward progression , live sperm count , membrane function , nuclear DNA integrity , capacity for cervical mucus penetration , linearity of spermatic movement , and amplitude of lateral sperm head movement ( all p < 0.0001 ) in the entire study population . In group 1A , there was a significant increase in total motility , live sperm count , membrane integrity and linearity of spermatic movement after 3 and 6 months of L-carnitine/L-acetylcarnitine treatment , and in capacity for cervical mucus penetration after 6 months of treatment , compared with baseline . Conclusion : Seminal carnitine concentration may be an appropriate marker of sperm and epididymal function . L-carnitine/L-acetylcarnitine treatment may be an effective therapy to improve mainly functional seminal parameters OBJECTIVES To examine whether a beneficial effect of N-acetylcysteine ( NAC ) on semen parameters and oxidative/antioxidant status in idiopathic male infertility exists . The production of reactive oxygen species is a normal physiologic event in various organs . However , overproduction of reactive oxygen species can be detrimental to sperm and has been associated with male infertility . METHODS Our study included 120 patients who had attended our clinic and were diagnosed with idiopathic infertility according to medical history and physical and seminal examination findings , as initial evaluations . The patients were divided r and omly into 2 groups . Those in the study group ( 60 men ) were given NAC ( 600 mg/d orally ) for 3 months ; the control group ( 60 men ) received a placebo . The oxidative status was determined by measuring the total antioxidant capacity , total peroxide and oxidative stress index in plasma sample s. The sperm parameters were evaluated after NAC treatment and were compared with those in the control group . RESULTS NAC had significant improving effects on the volume , motility , and viscosity of semen . After NAC treatment , the serum total antioxidant capacity was greater and the total peroxide and oxidative stress index were lower in the NAC-treated group compared with the control group . These beneficial effects result ed from reduced reactive oxygen species in the serum and reduced viscosity of the semen . No significant differences were found in the number or morphology of the sperm between the 2 groups . CONCLUSIONS We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility We performed a r and omized , prospect i ve , controlled , intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia ( 5–20 million/ml ) 6 months after retro grade embolization . Forty-two subjects were enrolled and r and omized in the study . Treated group ( 20 subjects ) was assigned to receive antioxidant therapy ( NAC 600 mg and vitamins – minerals ) . Untreated group ( 22 subjects ) received no adjunctive medical therapy and was used as controls . Our data were analyzed with an intention to treat strategy . A statistically significant increase in sperm count after antioxidant therapy was recorded ( P = 0.009 ) . After this therapy , no statistical differences in percentage of WHO class A motile sperm ( P = 0.752 ) and typical forms ( P = 0.926 ) were found . The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold ( OR = 20.1 ; CI 95 % = 1.05–43.2 ; P = 0.014 ) higher than a man who was untreated . No significant impact on spontaneous pregnancies was found after antioxidant therapy . Despite this preliminary data , we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males . However , this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months Objective : To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men . Subjects and Methods : Forty-five men with asthenozoospermia ( ≧40 % immotile sperm ) were r and omized into four therapy groups : zinc only : n = 11 ; zinc + vitamin E : n = 12 and zinc + vitamins E + C : n = 14 for 3 months , and non-therapy control group : n = 8 . Semen analysis was done according to WHO guidelines . Malone dialdehyde , tumour necrosis factor-α ( TNF-α ) , total antioxidant capacity , superoxide dismutase ( SOD ) and glutathione peroxidase were determined in the semen and serum . Antisperm antibodies IgG , IgM and IgA were evaluated by immunobeads . Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy . The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated . Results : Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde ( 8.8 vs. 1.8 mmol/l , p < 0.001 ) and TNF-α ( 60 vs. 12 pg/l , p < 0.001 ) , and low total antioxidant capacity ( 1.8 vs. 8.4 , p < 0.01 ) , SOD ( 0.8 vs. 3.1 , p < 0.01 ) and glutathione peroxidase ( 1.6 vs. 4.2 , p < 0.05 ) , compared to normozoospermia . Zinc therapy alone , in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress , sperm apoptosis and sperm DNA fragmentation index ( DFI ) . On the whole , there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation result ed in significantly lower DFI ( 14–29 % , p < 0.05 ) compared to zinc deficiency . Conclusion : Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress , apoptosis and sperm DNA fragmentation |
417 | 21,883,032 | This confirms that during VIT systemic reactions are significantly more frequent with honeybee venom compared with vespid venom , while there are no significant overall differences in systemic reactions between aqueous and depot extracts | INTRODUCTION The efficacy of venom immunotherapy ( VIT ) in patients with insect sting allergy is not question ed .
However , its safety , especially when honeybee is used , is a matter of concern . | Insect hypersensitivity is currently treated by immunization using whole-body extracts . We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity , as judged by venom skin test , histamine release and IgE antibody to venom . After six to 10 weeks of immunization , systemic reactions to stings occurred in seven of 12 , seven of 11 , and one of 18 patients treated with placebo , whole-body extract , and venom , respectively . Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy ( P less than 0.01 ) . The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy ; one reacted to a subsequent sting . We conclude that venom immunotherapy is clinical ly superior to therapy on whole-body extract or placebo 24 patients with honey bee sting allergy were treated with either honey bee venom ( HBV ) or monomethoxy polyethylene glycol-coupled HBV ( PEG-HBV ) in a double blind trial . Both treatments induced a strong increase in HBV-specific IgG antibodies in most patients . Immunotherapy with PEG-HBV was much better tolerated than that with HBV . Conversely , patients on HBV did considerably better during a sting challenge with a living honey bee . Only 4 developed a large local and one a mild systemic reaction compared to 7 large local and 3 moderate to severe systemic reactions in the PEG-HBV-group . A higher maintenance dose of PEG-HBV may still be well tolerated but prove more effective at reexposure Venom immunotherapy ( IT ) is a very effective method for the treatment of Hymenoptera venom allergy . We compared safety , efficacy , and modulation of specific immunologic parameters in 70 patients sensitized to Apis mellifera , treated for > or = 5 years with st and ardized quality ( SQ ) aqueous IT , either with a rush ( n = 20 ) or with a cluster ( n = 20 ) induction protocol , or with an SQ depot extract and a cluster induction protocol ( n = 30 ) . We made an open , noncontrolled study . Side effects were monitored and the effects of field stings during the maintenance phase of the treatment and after its interruption were recorded . Skin reactivity to Apis was measured by end point dilution and specific serum immunoglobulin E ( IgE ) were measured by a solid-phase-based assay . The depot IT was better tolerated than aqueous IT with rush induction . This was caused by mainly the lower frequency in the induction phase of systemic side effects ( 3.4 % versus 36.8 % [ p < 0.0041 ] on a " per patient " and 0.1 % versus 0.9 % [ p = 0.0092 ] on a " per dose " basis , respectively ) . The cluster protocol with the aqueous extract tended to be better tolerated that the rush protocol . About one-half of patients from each group were re-stung during the study and all suffered only minor discomfort . Reduction of skin reactivity and of serum-specific IgE was significant in the three groups ( p < 0.02 in all cases ) . SQ Depot IT to Apis venom allergy administered with a cluster protocol induces less side effects and is equally effective then IT with SQ aqueous extract administered with a rush protocol The incidence , time course and nature of systemic reactions to injections of bee and wasp venom during immunotherapy have been estimated in an open , prospect i ve , single centre study . One hundred and nine survivors of moderate to severe systemic reactions to stings from hymenoptera , received courses of bee or wasp venom by monthly subcutaneous injection for up to 3 years . Systemic reactions were recorded after 7.5 % of 946 weekly venom injections during the initial phase of treatment , and after 2.1 % of 1789 monthly maintenance injections . In both phases of treatment , reactions were more frequent after bee ( 17 % of initial phase , 7.8 % of maintenance treatment ) than after wasp ( 3 % of initial phase , 0.3 % of maintenance treatment ) venom injections . The percentage of patients experiencing at least one reaction was also higher for bee ( 46 % ) than for wasp ( 14 % ) sensitive patients . Over 80 % of reactions began within 30 min of injection , over 90 % within 1 h and only two ( 2 % ) , between 1 and 2 h , the remaining six ( 5.5 % ) starting more than 2 h after injection . Only 0.47 % of venom injections produced a systemic reaction which was severe enough to require adrenaline treatment . The female patients experienced more reactions ( 21 % of the wasp , 60 % of the bee , sensitive ) than the males ( 5.5 % wasp , 20 % bee ) . Age and atopy did not appear to be significant risk factors for systemic reactions . We conclude that wasp and bee venom immunotherapy in a conventional dosage regimen was generally well tolerated . No safety advantage was apparent in keeping the patients under observation for more than 1 h after injections . Reactions are more likely to occur during the initial phase of treatment , in women and after bee , rather than wasp , venom injections Background : The safety profile of venom immunotherapy is a relevant issue . We evaluated the frequency of severe adverse events ( SAE ) , associated risk factors , retrospective comparison of pretreatment protocol s including solely H1 receptor blockers and a combination of H1 and H2 receptor blockers during rush Hymenoptera venom immunotherapy . Methods : The study group comprised 118 patients . The treatment was initiated according to a 5-day rush protocol with the use of st and ardized venom allergens of either wasp or honeybee . Results : During the rush induction , side effects occurred in 18 patients ( 15.2 % ) , whereas SAE were present in 7 patients ( 5.9 % ) . Twelve out of 18 ( 66.6 % ) developed anaphylactic reactions on the fourth day of the rush protocol , with the majority of cases at a dose of 40 or 60 µg of the venom extract ( p = 0.001 ) . The frequency of SAE was also significantly higher on the fourth day than thereafter ( p = 0.0001 ) as well as in patients allergic to bee venom ( p = 0.049 ) . All systemic side effects were more frequent in women ( p = 0.0065 ) . However , this relation was not true when SAE were consider ( p = 0.11 ) . A higher percentage of SAE was observed in the subjects pretreated with both H1 and H2 receptor antagonists than in those pretreated with H1 blocker only ( 8.8 vs. 4.1 % ) ; however , the difference was not significant . Conclusions : Considerable severity of allergic adverse events requires particular attention to patients allergic to bee venom and during rush phase , especially when rapidly increasing doses are administered . Pretreatment with H2 blockers is debatable and warrants further investigation This prospect i ve study over 3 years investigated the safety , immunogenicity , and effectiveness of immunotherapy ( IT ) with aluminum hydroxide adsorbed insect venom extracts ( Alutard SQ , ALK Laboratories ) m patients with previous , severe , systemic , IgE‐mediated , anaphylactic reactions to Hymenoptera stings . Seventeen patients were treated with honeybee venom ( BV ) , 13 with yellow‐jacket venom ( YJV ) , and 5 with both . No severe reactions to IT were noted . Only 3 BV‐allergic patients experienced mild systemic reactions of grade s I or II ( 1 per 139 injections ) during the increase phase BACKGROUND Venom immunotherapy rapidly reduces the risk of a systemic sting reaction in adults from 30 % to 70 % to less than 2 % . When venom immunotherapy is stopped after 5 years or longer , the risk of a systemic sting reaction is 5 % to 15 % during the first few years after stopping treatment . It is uncertain whether systemic sting reactions will occur more than 5 years after discontinuing venom immunotherapy and whether treatment can be safely stopped in some patients after less than 5 years . OBJECTIVE The purpose of this study is to estimate the risk of systemic reaction to a sting 10 years after discontinuing treatment and the relative risk after 3 years of treatment compared with that after 5 years or more of treatment . METHODS Among all patients who had venom immunotherapy at our center , we identified 395 patients who stopped treatment : some had dropped out of therapy early ( 6 - 24 months ) , some stopped after 3 to 4 years , and most completed 5 years or more of venom immunotherapy and were advised to stop by the allergist ( many as part of our reported studies of discontinuing venom immunotherapy ) . RESULTS Contact was made with 194 patients , including telephone interviews for sting history and requests to visit the office for skin testing and blood sampling . Of these patients , 74 had been included in our original study of patients who had 5 years or more of venom immunotherapy and had sting challenges after 1 to 5 years off venom immunotherapy , as previously reported . Of the 74 in that original study , 61 were reached for this survey , and 30 reported recent stings , with 5 systemic sting reactions . Another 133 patients who had stopped venom immunotherapy were reached : 82 had 5 or more years of venom immunotherapy , 20 had 3 to 4 years of venom immunotherapy , and 31 had less than 2 years of venom immunotherapy . Of 51 patients stung from this group , 27 had 5 or more years of venom immunotherapy ( no systemic sting reactions ) , and 24 had less than 5 years of venom immunotherapy ( 3 systemic sting reactions ) . We have now observed a total of 113 patients who had 5 or more years of venom immunotherapy and were stung after stopping . Sixteen ( 14 % ) had systemic sting reactions ; most were mild , but 4 were severe . Systemic sting reactions occurred in 12 ( 10.7 % ) of 112 patients stung in the first 4 years off venom immunotherapy and 5 ( 10 % ) of 50 stung more than 5 years off venom immunotherapy . In 4 of 8 patients with current systemic sting reactions , the skin test response was negative , although the venom-IgE response was positive at the previous encounter . All systemic sting reactions were similar in pattern and severity to prevenom immunotherapy reactions in the same patient . CONCLUSIONS We conclude that the risk of systemic sting reactions when venom immunotherapy is stopped after 5 years or longer remains in the reported range of 5 % to 15 % in the 5 to 10 years after stopping venom immunotherapy . This risk of systemic sting reactions does not seem to decrease over time , unlike the progressive decline in immunologic markers ( skin test and venom-IgE responses ) . To prospect ively assess the risk of recurrent systemic sting reactions , there is a need for sting challenge studies of patients who have been off venom immunotherapy for 5 to 10 years and patients who have stopped venom immunotherapy after just 3 to 4 years treatment Venom immunotherapy ( VIT ) with aqueous extracts is considered a life-saving treatment in insect allergy , but systemic side effects are quite common , especially in patients sensitized to Apis mellifera venom . Only a few studies are available regarding depot VIT administered according to the st and ard weekly schedule , while no data are available for cluster VIT with depot preparations . This study was design ed to compare the tolerance of aqueous cluster or rush VIT versus cluster depot VIT in patients sensitized to Apis mellifera . Fifty-five patients with a history of systemic reaction ( grade II to IV according to Müller ) after an Apis mellifera sting were divided at r and om into 3 groups . Forty patients were treated with aqueous VIT ( 20 according to a cluster schedule and 20 according to a rush schedule ) and 15 with Depot VIT according to a cluster schedule . All local and systemic side effects were recorded . Four patients belonging to the aqueous-cluster , 4 belonging to the aqueous-rush , and 1 belonging to the depot-cluster schedule had large local reactions after VIT ( p < 0.009 ) . Systemic side effects were recorded in 1 , 7 and 0 patients ( p < 0.003 ) respectively . No statistically significant difference was found between the two cluster regimens in the frequency of side effects . Depot VIT administered according to a cluster schedule was well tolerated , and its tolerance is better than aqueous-rush VIT for Apis mellifera BACKGROUND Hymenoptera venom hypersensitivity is an epidemiologically important problem . The only effective treatment in the management of venom-allergic patients with a history of generalized reactions to insect sting is specific immunotherapy . OBJECTIVE To demonstrate safety and effectiveness of a modified ultrarush desensitization protocol in venom-allergic patients . METHODS Fifty-seven patients with Hymenoptera venom allergy underwent a specific 1-day ultrarush desensitization by the subcutaneous route , reaching the cumulative dose of 101.1 microg in 2.5 hours . The maintenance dose ( 100 microg ) was administered after 15 days and thereafter once a month . Patients were followed up for a year . Antihistamines were withheld for 15 days before and during desensitization to not underestimate the incidence of adverse effects . RESULTS All patients but I completed the ultrarush desensitization . ( This patient discontinued the treatment because of a hypertensive crisis not related to the desensitization . ) The treatment caused a rapid variation of immunological parameters ( IgE , IgG4 ) since the 15th day . After the desensitization , skin prick test results became negative in 15 patients ( 27 % , decrease of 3.5 log ) , whereas they decreased in 14 patients ( 25 % , decrease of 1 log ) . Sixty-four percent showed no adverse effects . Only 7 % had a mild systemic reaction . CONCLUSIONS Ultrarush desensitization is an effective and safe therapy in the management of patients with Hymenoptera venom allergy . In fact , it provides a faster tolerance , without significant differences regarding incidence of severe adverse effects , compared with traditional and rush protocol s. It can be adopted for all patients , even children and teenagers The prevalence of insect venom allergy in the European population is approximately 5 % . Hymenoptera venom allergy is an important epidemiological problem . Ten to 40 deaths are reported annually in Germany . In contrast to conventional dose increase schedules lasting a minimum of 5 days , shorter protocol s reduce the patient 's stay in the hospital and provide an earlier protection toward stings . Clinical studies on ultrarush protocol s have been published for adult patients , but very little data are currently available for children . Therefore , we investigated the safety and tolerability of a shortened insect venom immunotherapy ( VIT ) in children and adolescents . Forty-three children and adolescents ( aged 4 - 18 years ) with insect venom allergy were treated in this study . Five children were hyposensitized according to the ultrarush protocol with nine injections ( as suggested by Brehler et al. ( Safety of a two-day ultrarush insect VIT protocol in comparison with protocol s of longer duration and involving a larger number of injections . J Allergy Clin Immunol 105:1231 - 1235,2000 ) ; 38 children received the modified ultrarush schedules with only eight subcutaneous injections . With both protocol s the maintenance dose ( 100 microg ) was achieved in 24 hours . Twenty-five patients ( 58.1 % ) showed no reaction after the injections . In 11 patients ( 25.6 % ) , extensive erythema ( > 5 cm , maximum of 20 cm ) was found at the injection site . Erythema and edema ( > 5 cm , maximum of 15 cm ) were observed in seven patients ( 16.2 % ) . The maintenance dose was well tolerated , with no systemic reaction in any patient . The modified ultrarush protocol for insect VIT used in this study showed very good tolerability and safety in children and adolescents . This dose regimen can increase compliance by shortening inpatient stay and reduces hospital costs Venom immunotherapy ( VIT ) for Hymenoptera allergy is accepted as safe and effective . However , widely varying success rates and frequencies of side effects are reported . Differences between various Hymenoptera species could account for these diverging results . We therefore analyzed 205 patients with a history of systemic allergic reactions to either honeybee ( 148 patients ) or yellow jacket stings ( 57 patients ) during VIT . All patients had a positive skin test to the respective venom before VIT , were monitored for side effects of VIT , and su bmi tted to a sting challenge while they were receiving VIT . Patients with honeybee-venom allergy had a higher sensitivity in both skin tests ( p less than 0.05 ) and RAST ( p less than 0.001 ) than patients with yellow jacket-venom allergy . They developed systemic side effects to VIT injections significantly more often ( 41 % versus 25 % ; p less than 0.01 ) and also reacted more frequently to the sting challenge ( 23 % versus 9 % ; p less than 0.01 ) than patients with yellow jacket-venom allergy . We conclude that results obtained from studies on the allergy to one Hymenoptera venom can not be extrapolated to allergies to other Hymenoptera venoms BACKGROUND Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions . OBJECTIVE The efficacy of pretreatment with an H1/H2-antagonist combination , H1-antagonist alone , or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared . METHODS In a prospect i ve , r and omized , double-blind , placebo-controlled study , 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following : 120 mg of terfenadine plus 300 mg of ranitidine , 120 mg of terfenadine alone , or placebo . The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks . RESULTS In seven patients ( 6 % ) , six in the placebo group and one in the terfenadine group , systemic side effects required cessation of therapy ( p = 0.005 ) . Subjective symptoms occurred in four patients ( 10 % ) in the terfenadine plus ranitidine group and in three patients ( 7 % ) in the terfenadine group . Regarding local reactions , significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema ( 29 % , 29 % , and 49 % ) , edema ( 24 % , 18 % , and 41 % ) , and pruritus ( 13 % , 11 % , and 31 % ) at week 1 ( p < 0.05 ) . This therapeutic benefit was limited to the first 4 weeks of treatment . Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone . CONCLUSIONS Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy BACKGROUND Venom immunotherapy is an effective method for the treatment of Hymenoptera venom allergy . Different extracts and treatment schedules are available . OBJECTIVE To compare the safety and efficacy of immunotherapy in 3 cohorts of patients sensitized to Vespula species . METHODS In this open study , 43 patients were treated with a subcutaneous aqueous extract for induction and maintenance ( AA ) , 34 with a subcutaneous depot extract for induction and maintenance ( DD ) , and 29 with subcutaneous aqueous and subcutaneous depot extracts for induction and maintenance , respectively ( AD ) . Cluster schedules were followed to reach maintenance , and adverse effects during treatment and after naturally occurring stings were recorded . RESULTS Depot immunotherapy was better tolerated mainly owing to the lower frequency of local adverse effects in the induction phase ( 5.9 % vs 42.5 % and 1.3 % vs 5.1 % on a per patient and per dose basis , respectively ; P < .001 for both ) and for effects occurring within 60 minutes after vaccination ( 2.9 % vs 19.2 % and 0.2 % vs 2.8 % on a per patient and per dose basis ; P = .03 and P < .001 , respectively ) . Furthermore , 19 of 20 AA , 9 of 9 AD , and 10 of 10 DD patients who were restung experienced only minor local effects . CONCLUSIONS Venom immunotherapy is efficacious . Although there was no decrease in systemic reactions , depot immunotherapy to Vespula venom induced fewer early local adverse effects . Patients undergoing an induction phase with an aqueous extract can benefit from switching to a depot extract during maintenance . Increasing the flexibility of the immunization schedules may improve compliance with this potentially lifesaving treatment BACKGROUND Rapid venom immunotherapy regimens have been developed to provide safe protection to individuals who have experienced Hymenoptera anaphylaxis by administering greater than 50 micrograms of venom over two to three hours on treatment day 1 . A rapid venom immunotherapy protocol which consisted of administration of a cumulative dose of 58.55 micrograms of each venom on treatment day 1 followed by an accelerated build-up over 3 weeks to a final maintenance dose of 100 micrograms per venom was developed by our group in 1984 . OBJECTIVE We report our 10-year cumulative experience with this rapid venom immunotherapy regimen . METHODS Seventy-seven venom-allergic patients received a cumulative dose of 58.55 micrograms per venom on treatment day 1 in an ambulatory care setting . Rapid venom immunotherapy was assessed for safety . A cost analysis was performed to compare rapid venom immunotherapy to a modified rush immunotherapy regimen . RESULTS Four patients ( 5.2 % ) , experienced mild systemic reactions consisting of diffuse urticaria on day 1 . Treatment was otherwise well tolerated . Resting events occurred in 21 patients , a mean number of 12 months ( range : 3 days to 48 months ) after treatment , without systemic reactions . CONCLUSIONS This experience confirms that rapid venom immunotherapy is safe to administer in an ambulatory setting and should be considered especially for patients during the stinging insect season when rapid protection is required Thirty‐two patients with previous systemic allergic reaction to yellow jacket stings were r and omly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom : 1 ) extract adsorbed to aluminium hydroxide ( Alutard ® ‐SQ ) , 2 ) Pharmalgen ® extract or 3 ) non‐adsorbed extract from Allergologisk Laboratorium ( ALK aq . ) . Regular examinations showed a decrease in skin prick test size in nearly all patients . Specific IgE‐antibody ( RAST and CRIE scores ) showed a similar , but not significant tendency to decrease in all three groups . Specific IgG‐antibody increased considerably in the Alutard group only ; after 2 years , however , no difference could be detected between the three groups . During dose increase , patients treated with ALK aq . generally had smaller local reactions to injections than those treated with Pharmalgen . Few systemic reactions occurred in all three groups . Nineteen patients treated for 21/2–31/2 years were challenged in‐hospital with stings from yellow jackets . No systemic and only minor local reactions occurred . Consequently , with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated BACKGROUND Severe side effects during venom immunotherapy ( VIT ) are associated with a variety of risk factors . OBJECTIVE Our aim was to evaluate the association of baseline serum tryptase concentration ( BTC ) and of other parameters , which are routinely recorded during patient evaluation , with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT . METHODS In this observational prospect i ve multicenter study , we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT . Data were collected on tryptase concentration , age , sex , culprit insect , cardiovascular medication , degree of preceding sting reaction , preventive antiallergic medication before therapy , time between last preceding sting reaction and VIT , venom specific IgE concentration , and type of buildup procedure . Relative rates were calculated with generalized additive models . RESULTS Fifty-seven patients ( 8.4 % ) required an emergency intervention during buildup because of a severe systemic reaction . The frequency of interventions increased significantly with higher BTC ( log-linear association ; adjusted odds ratio , 1.56 ; 95 % CI , 1.15 - 2.11 ; P < .005 ) . The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom ( for bee VIT , no significant association ; for vespid VIT , log-linear association ; adjusted odds ratio , 2.33 ; 95 % CI , 1.28 - 4.26 ; P = .005 ) . The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy . CONCLUSION Before vespid VIT , measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects . Patients with bee venom allergy require a particularly high degree of surveillance during VIT |
418 | 25,683,111 | During rest and activities below shoulder height , no clear differences in mean Upper Trapezius ( = UT ) EMG activity exist between patients with idiopathic neck pain and a healthy control group .
During overhead activities , no conclusion for scapular EMG amplitude can be drawn as a large variation of results were reported .
Adaptation strategies during overhead tasks are not the same between studies . | It is proposed that altered scapular muscle function can contribute to abnormal loading of the cervical spine .
However , it is not clear if patients with idiopathic neck pain show altered activity of the scapular muscles .
The aim of this paper was to systematic ally review the literature regarding the differences or similarities in scapular muscle activity , measured by electromyography ( = EMG ) , between patients with chronic idiopathic neck pain compared to pain-free controls . | Aim . This study investigates consequences of chronic neck pain on muscle function and the rehabilitating effects of contrasting interventions . Methods . Women with trapezius myalgia ( MYA , n = 42 ) and healthy controls ( CON , n = 20 ) participated in a case-control study . Subsequently MYA were r and omized to 10 weeks of specific strength training ( SST , n = 18 ) , general fitness training ( GFT , n = 16 ) , or a reference group without physical training ( REF , n = 8) . Participants performed tests of 100 consecutive cycles of 2 s isometric maximal voluntary contractions ( MVC ) of shoulder elevation followed by 2 s relaxation at baseline and 10-week follow-up . Results . In the case-control study , peak force , rate of force development , and rate of force relaxation as well as EMG amplitude were lower in MYA than CON throughout all 100 MVC . Muscle fiber capillarization was not significantly different between MYA and CON . In the intervention study , SST improved all force parameters significantly more than the two other groups , to levels comparable to that of CON . This was seen along with muscle fiber hypertrophy and increased capillarization . Conclusion . Women with trapezius myalgia have lower strength capacity during repetitive MVC of the trapezius muscle than healthy controls . High-intensity strength training effectively improves strength capacity during repetitive MVC of the painful trapezius muscle This study aim ed at investigating whether patients with neck – shoulder complaints from different aetiologies ( work-related musculo-skeletal disorders , WMSD ; whiplash associated disorders , WAD ) show comparable muscle activation patterns , characterised by higher activation and lower relaxation levels of the trapezius muscles compared to healthy controls . Twenty healthy controls , 21 WMSD and 20 WAD patients with non-acute neck-shoulder pain were recruited for this cross-sectional study . Surface electromyography ( sEMG ) recordings were performed at the upper trapezius muscles during reference contractions , st and ardised computer tasks ( typing and unilateral stress task ) , and rest measurements . sEMG was continuously recorded during these measurements . Outcome measures were root mean square ( RMS ) to study muscle activity , and relative rest time ( RRT ) to study muscle relaxation . Statistical analysis comprised the bootstrap technique and Kruskall – Wallis tests . Results showed no clear evidence for abnormal muscle activation patterns in WMSD and WAD patients compared to healthy controls . However , a tendency was observed for higher RMS levels during the reference contractions and computer tasks in both patient groups compared to healthy controls , and lower RRT levels at the non-dominant side during stress . Both patient groups also showed larger variability in RMS and RRT values . This variability has more often been reported in literature and may suggest the existence of subgroups of pain patients with corresponding different muscle activation patterns not related to aetiology . Future research may focus on identifying these subgroups of patients with neck-shoulder pain The aim of this investigation was to study female workers active in the labour market for differences between those with trapezius myalgia ( MYA ) and without ( CON ) during repetitive pegboard ( PEG ) and stress ( STR ) tasks regarding ( 1 ) relative muscle load , ( 2 ) trapezius muscle blood flow , ( 3 ) metabolite accumulation , ( 4 ) oxygenation , and ( 5 ) pain development . Among 812 female employees ( age 30–60 years ) at 7 companies with high prevalence of neck/shoulder complaints , clinical examination identified 43 MYA and 19 CON . At rest , during PEG , and STR the trapezius muscle was measured using ( 1 ) EMG and MMG , ( 2 ) microdialysis , and ( 3 ) NIRS . Further , subjective pain ratings were scored ( VAS ) . EMGrms in % MVE ( Maximal Voluntary EMG-activity ) , was significantly higher among MYA than CON during PEG ( 11.74 ± 9.09 vs. 7.42 ± 5.56%MVE ) and STR ( 5.47 ± 5.00 vs. 3.28 ± 1.94%MVE ) . MANOVA showed a group and time effect regarding data from the microdialysis : for MYA versus CON group differences demonstrated lower muscle blood flow and higher lactate and pyruvate concentrations . Potassium and glucose only showed time effects . NIRS showed similar initial decreases in oxygenation with PEG in both groups , but only in CON a significant increase back to baseline during PEG . VAS score at rest was highest among MYA and increased during PEG , but not for CON . The results showed significant differences between CON and MYA regarding muscle metabolism at rest and with PEG and STR . Higher relative muscle load during PEG and STR , insufficient muscle blood flow and oxygenation may account for the higher lactate , pyruvate and pain responses among MYA versus CON Abstract Objectives . The purpose of this prospect i ve laboratory study was to follow newly employed workers in the fish or poultry industry for 6 months and investigate possible changes in sensory manifestations and motor performance during low load , repetitive work simulation . It was investigated whether the changes were an effect of employment duration and of development of neck – shoulder complaints . Methods . Twelve newly employed female filleting employees without any sign of neck – shoulder tenderness/pain at the time of employment of 0 months took part in two laboratory recording sessions planned within 1 month of employment and after 6 months of employment at the plant . After 6 months , six workers out of 12 had developed pain and /or tenderness in the neck – shoulder region . The recording sessions evaluated sensory-motor aspects by measuring pressure pain threshold , work-task timing , cutting forces , surface electromyographic activity of four shoulder muscles , displacement of the centre of pressure , and 3D movements of the arm and trunk during simulation of low load , repetitive filleting . Results . Effects due to the duration of employment were observed in both groups , i.e. decreased sensibility to pressure , decrease in the duration of the work cycle , increased arm starting position with respect to the upright position , and decreased range of motion of the arm and trunk ( P<0.05 ) after 6 months . Among the workers with neck – shoulder complaints , increased sensibility to pressure , lower force level , higher electromyographic activity , decreased amplitude of arm movement , and increased trunk posture and movement amplitude ( P<0.05 ) were observed , compared with workers without complaints . Conclusions . Differences in terms of sensory manifestations and motor control strategy were seen after 6 months of employment with or without neck – shoulder complaints . In general , changes in sensory manifestations and motor control strategy after 6 months work were most likely of importance , as they underlined a learning process as employment duration increased . Moreover , the present sensory – motor changes observed among workers with neck – shoulder complaints highlighted the potential physical risk factors associated with low load , repetitive work Abstract Little is known about the mechanisms leading to chronic neck-shoulder musculoskeletal disorders ( MSD ) . The aim of the present study was to investigate and compare motor function during controlled , low load , repetitive work together with chronic or acute experimental neck-shoulder pain . The clinical study was performed on workers with ( n = 12 ) and without ( n = 6 ) chronic neck-shoulder pain . In the experimental study , experimental muscle pain was induced in healthy subjects by intra-muscular injection of hypertonic saline into the trapezius muscle ( n = 10 ) . The assessed parameters related to motor performance were : work task event duration , cutting forces , surface electromyogram ( EMG ) activity in four shoulder muscles , displacement of the centre of pressure , and arm and trunk 3D movements . For controlled cutting force levels , chronic and acute experimental pain provoked a series of changes : a decreased working rhythm and a protective reorganisation of muscle synergy ( experimental study ) , higher EMG frequency contents which may indicate altered motor unit recruitment , and greater postural activity and a tendency towards increased arm and trunk movements . These pain-related changes can play a role in the development of MSD . The present clinical and experimental study demonstrated similar interactions between motor co-ordination and neck-shoulder pain in occupational setting s. We therefore suggest that this experimental model can be used to study mechanisms related to MSD . Information on such modulatory processes may help in the design of new strategies aim ed at reducing the development of MSD The aim of the present study was to investigate reactions in trapezius muscle blood flow ( MBF ) , muscle activity , heart rate variability ( HRV ) and systemic blood pressure ( BP ) to autonomic tests in subjects with chronic neck – shoulder pain and healthy controls . Changes in muscle activity and blood flow due to stress and unfavourable muscle loads are known underlying factors of work-related muscle pain . Aberration of the autonomic nervous system ( ANS ) is considered a possible mechanism . In the present study , participants ( n = 23 Pain , n = 22 Control ) performed autonomic tests which included a resting condition , static h and grip test ( HGT ) at 30 % of maximal voluntary contraction , a cold pressor test ( CPT ) and a deep breathing test ( DBT ) . HRV was analysed in time and frequency domains . MBF and muscle activity were recorded from the upper trapezius muscles using photoplethysmography and electromyography ( EMG ) . The pain group showed reduced low frequency-HRV ( LF ) and SDNN during rest , as well as a blunted BP response and increased LF-HRV during HGT ( ∆systolic 22 mm Hg ; ∆LF(nu ) 27 % ) compared with controls ( ∆systolic 27 ; ∆LF(nu ) 6 % ) . Locally , the pain group had attenuated trapezius MBF in response to HGT ( Pain 122 % Control 140 % ) with elevated trapezius EMG following HGT and during CPT . In conclusion , only HGT showed differences between groups in systemic BP and HRV and alterations in local trapezius MBF and EMG in the pain group . Findings support the hypothesis of ANS involvement at systemic and local levels in chronic neck – shoulder pain The present study investigated the effect of chronic neck muscle pain ( defined as trapezius myalgia ) on neck/shoulder muscle function during concentric , eccentric and static contraction . Forty-two female office workers with trapezius myalgia ( MYA ) and 20 healthy matched controls ( CON ) participated . Isokinetic ( -60 , 60 and 180 degrees s(-1 ) ) and static maximal voluntary shoulder abductions were performed in a Biodex dynamometer , and electromyography ( EMG ) obtained in the trapezius and deltoideus muscles . Muscle thickness in the trapezius was measured with ultrasound . Pain and perceived exertion were registered before and after the dynamometer test . The main findings were that shoulder abduction torque ( at -60 and 60 degrees s(-1 ) ) and trapezius EMG amplitude ( at -60 , 0 and 60 degrees s(-1 ) ) were significantly lower in MYA compared with CON ( p<0.001 - 0.05 ) . Deltoideus EMG and trapezius muscle thickness were not significantly different between the groups . While perceived exertion increased in both groups in response to the test ( p<0.0001 ) , pain increased in MYA only ( p<0.0001 ) . In conclusion , having trapezius myalgia was associated with decreased strength capacity and lowered activity of the painful trapezius muscle . The most consistent differences-in terms of both torque and EMG-were found during slow concentric and eccentric contractions . Activity of the synergistic pain free deltoideus muscle was not significantly lower , indicating specific inhibitory feedback of the painful trapezius muscle only . Parallel increase in pain and perceived exertion among MYA were observed in response to the maximal contractions , emphasizing that heavy physical exertion provokes pain increase only in conditions of myalgia Abstract This cross-sectional study aim ed at investigating the influence of occupational exposure to static and highly repetitive work involving the neck and shoulder muscles , myalgia of and tender point in the trapezius muscle on biomechanical output , and electromyogram ( EMG ) variables ( mean frequency MNF , signal amplitude and ability to relax ) during maximal forward flexions of the shoulder muscles . Groups of 25 cleaners suffering from chronic myalgia of the trapezius muscle , 25 cleaners free from myalgia of the trapezius muscle and 21 teachers performed 150 forward flexions using an isokinetic dynamometer . Perception of fatigue was reported and surface EMG was recorded from four muscles during the endurance test . The cleaners were stronger than the teachers . Myalgia was associated with lower levels of endurance and a high degree of perceived fatigue . The ability to relax the trapezius muscle decreased with age and was even lower in cleaners with and without myalgia . Higher MNF of the deltoid muscle but not of the trapezius muscle was found in the group suffering from myalgia compared to the groups free from myalgia . This cross-sectional study indicated that myalgia of the trapezius muscle did not influence the strength but did influence the endurance of the forward flexor muscles of cleaners . The observed decrease in the ability to relax the trapezius muscle in cleaners compared to healthy teachers might be indicative of a future insufficiency in the muscle . Prospect i ve studies are needed to define the significance of the results presented here The aim of this prospect i ve study was to detect a possible development of trapezius myalgia likely to be work-related in initially healthy female packers . Symptoms were recorded on a five-step intensity scale in a daily diary and in an interview at ten-week intervals . All of the subjects were interviewed concerning assumed risk factors during work and leisure time , and a clinical examination was performed . Within their first year of employment , 17 of 30 subjects developed work-related trapezius myalgia of sufficient intensity to be classified as patients . The median time before a clinical ly confirmed patient status was 23 ( range 6 - 51 ) weeks . The symptoms showed a fluctuating pattern , decreasing on the weekends and during some holidays . In conclusion , likely work-related trapezius myalgia of a nonchronic character showed a high one-year cumulative incidence at a plant with repetitive light work Chronic neck pain may increase the transmitter activity of neuropeptides in the upper cervical medulla causing impairment of the blood flow in the local muscle because of a lack of vasodilatatory substances excreted axonally . We have been using a new single-fibre technique for clinical determination of the microcirculation ( LDF ) in the trapezius muscles in relation to electromyography ( EMG ) . This study pertains to the 76 patients ( 46 women and 30 men ) who received a final diagnosis of chronic trapezius myalgia out of a total series of 300 cases with chronic neck pain which had been remitted to the National Insurance Administration Hospital in Tranås , Sweden , because their complaints interfered with their working ability . The purpose was to derive more objective medical information upon which to base rehabilitation . Sixty percent had continuous pain and 40 % had pain after physical effort , or at work . Twenty healthy women volunteered to participate as a normal control group . The right and left trapezius muscles of all individuals were examined simultaneously with laser-Doppler flowmetry ( LDF ) and surface EMG during a fatiguing series of stepwise-increased contractions , each of 1 min duration with 1 min rest in between . The most painful side was compared with the opposite side in all patients and , in the female patients , also with the right shoulder of the healthy control women . The patients showed consistently low local blood flow in the painful side . The difference was statistically significant at low contraction intensities . Muscle tension was somewhat elevated , as evidence d by a slight increase of the rms-EMG that was statistically significant at high contraction intensities . The mean power frequency ( MPF ) of the EMG showed no change . The lowered local blood flow was not explained by a changed intramuscular pressure which is low in the trapezius during ordinary activities that do not normally impair the local blood flow ( Larsson , S-E. , Cai , H. and ( Oberg , P.A. , Microcirculation in the upper trapezius muscle during varying levels of static contraction , fatigue and recovery in healthy women . A study using percutaneous laser-Doppler flowmetry and surface electromyograpy , Eur . J. Appl . Physiol . , 66 ( 1993 ) 483 - 488 ) . We conclude that an impaired regulation of the microcirculation in the local muscle is of central importance in chronic trapezius myalgia , causing nociceptive pain which can be differentiated objective ly from neuralgic neck-shoulder pain by the atraumatic technique described |
419 | 28,905,008 | RESULTS Most of the review ed articles presented satisfactory results related to the prevention of surgical inflammation in patients undergoing resection of CRC when using strains of Lactobacillus genus , predominantly .
CONCLUSIONS Probiotics are suggested to prevent surgical inflammation of CRC , at the same time that the combination of particular microorganisms administered is beneficial to the treatment and surgical recovery | BACKGROUND Infection following abdominal surgery remains a major factor in morbidity among colorectal cancer ( CRC ) patients .
Probiotic therapy has been suggested to improve the clinical and laboratory outcome of patients undergoing gastrointestinal surgery .
The aim of this study was to investigate the efficacy of probiotic lactic acid bacteria in patients with CRC in the pre- and postoperative phases . | Background The gut microbiota is interlinked with obesity , but direct evidence of effects of its modulation on body fat mass is still scarce . We investigated the possible effects of Bifidobacterium animalisssp . lactis 420 ( B420 ) and the dietary fiber Litesse ® Ultra polydextrose ( LU ) on body fat mass and other obesity-related parameters . Methods 225 healthy volunteers ( healthy , BMI 28–34.9 ) were r and omized into four groups ( 1:1:1:1 ) , using a computer-generated sequence , for 6 months of double-blind , parallel treatment : 1 ) Placebo , microcrystalline cellulose , 12 g/d ; 2 ) LU , 12 g/d ; 3 ) B420 , 1010 CFU/d in microcrystalline cellulose , 12 g/d ; 4 ) LU + B420 , 12 g + 1010 CFU/d . Body composition was monitored with dual-energy X-ray absorptiometry , and the primary outcome was relative change in body fat mass , comparing treatment groups to Placebo . Other outcomes included anthropometric measurements , food intake and blood and fecal biomarkers . The study was registered in Clinical trials.gov ( NCT01978691 ) . Findings There were marked differences in the results of the Intention-To-Treat ( ITT ; n = 209 ) and Per Protocol ( PP ; n = 134 ) study population s. The PP analysis included only those participants who completed the intervention with > 80 % product compliance and no antibiotic use . In addition , three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement . There were no significant differences between groups in body fat mass in the ITT population . However , LU + B420 and B420 seemed to improve weight management in the PP population . For relative change in body fat mass , LU + B420 showed a − 4.5 % ( − 1.4 kg , P = 0.02 , N = 37 ) difference to the Placebo group , whereas LU ( + 0.3 % , P = 1.00 , N = 35 ) and B420 ( − 3.0 % , P = 0.28 , N = 24 ) alone had no effect ( overall ANOVA P = 0.095 , Placebo N = 35 ) . A post-hoc factorial analysis was significant for B420 ( − 4.0 % , P = 0.002 vs. Placebo ) . Changes in fat mass were most pronounced in the abdominal region , and were reflected by similar changes in waist circumference . B420 and LU + B420 also significantly reduced energy intake compared to Placebo . Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU + B420 group and in the overall population . There were no differences between groups in the incidence of adverse events . Discussion This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass . B420 and LU + B420 also reduced waist circumference and food intake , whereas LU alone had no effect on the measured outcomes Objective To evaluate the potential clinical , metabolic , and economic advantages of enteral nutrition over total parenteral nutrition . Design Prospect i ve , r and omized clinical trial . Setting Department of surgery in a university hospital . Patients Two hundred and fifty-seven patients with cancer of the stomach ( n = 121 ) , pancreas ( n = 110 ) , or esophagus ( n = 26 ) were r and omized to receive postoperative total parenteral nutrition ( TPN group , n = 131 ) or early enteral nutrition ( EEN group , n = 126 ) . The nutritional goal was 25 kcal/kg/day . The two nutritional formulas were isocaloric and isonitrogenous , and they were continued until oral intake was at least 800 kcal/day . Measurements Morbidity , mortality , length of hospital stay , and treatment costs were evaluated in all patients . In 40 consecutive patients , selected nutritional , immunologic and inflammatory variables were studied . Moreover , intestinal oxygen tension was evaluated by micropolarographic implantable probes . Main Results The nutritional goal was reached in 100/126 ( 79.3 % ) patients in the EEN group and in 128/131 ( 97.7 % ) patients in the TPN group ( p < .001 ) . In the EEN group , hyperglycemia ( serum glucose , > 200 mg/dL ) was observed in 4.7 % of the patients vs. 9.1 % in the TPN group ( p = NS ) . Alteration of serum electrolyte levels was 3.9 % in the EEN group vs. 13.7 % in the TPN group ( p < .01 ) . No significant difference was found in nutritional , immunologic , and inflammatory variables between the two groups . The overall complication rate was similar ( 40.4 % for TPN vs. 35.7 % , for EEN;p = .52 ) . No difference was detected for either infectious or noninfectious complications , length of hospital stay , and mortality . From postoperative day 5 , intestinal oxygen tension recovered faster in the EEN group than in the TPN group ( 43 ± 5 mm Hg vs. 31 ± 4 mm Hg at day 7;p < .001 ) . EEN was four-fold less expensive than TPN ( $ 25 vs. $ 90.60/day , respectively ) . Conclusion EEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinical ly require postoperative artificial nutrition BACKGROUND The clinical value of synbiotics in patients undergoing esophagectomy remains unclear . This study investigated the effects of synbiotics on intestinal microflora and surgical outcomes in a clinical setting . METHODS We studied 70 patients with esophageal cancer who were scheduled to undergo esophagectomy . They were r and omly allocated to 2 groups : 1 group received synbiotics before and after surgery , and the other did not . Fecal microflora and organic acid concentrations were determined . Postoperative infections , abdominal symptoms , and duration of systemic inflammatory response syndrome ( SIRS ) were recorded . RESULTS Of the patients , 64 completed the trial ( synbiotics , 30 ; control , 34 ) . The counts of beneficial bacteria and harmful bacteria in the group given synbiotics were significantly larger and smaller , respectively , than those in the control group on postoperative day ( POD ) 7 . The concentrations of total organic acid and acetic acid were higher in the synbiotics group than in the control group ( P < .01 ) , and the intestinal pH in the synbiotics group was lower than that in the control ( P < .05 ) on POD 7 . The rate of infections was 10 % in the synbiotics group and 29.4 % in the control group ( P = .0676 ) . The duration of SIRS in the synbiotics group was shorter than in the control group ( P = .0057 ) . The incidence of interruption or reduction of enteral nutrition by abdominal symptoms was 6.7 % in the synbiotics group and 29.4 % in the control group ( P = .0259 ) . CONCLUSION Perioperative administration of synbiotics in patients with esophagectomy is useful because they suppress excessive inflammatory response and relieve uncomfortable abdominal symptoms through the adjustment of the intestinal microfloral environment Apart from the intestinal environment , inulin induces physiological effects , which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides . We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 ( GLP-2 ) levels in healthy young subjects . Twenty healthy , young male volunteers completed a r and omized , double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods ( 11 % inulin-enriched or control pasta ) , with an 8-week washout period in between . The intestinal barrier function was assessed by lactulose-mannitol excretion in urine . Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay . In the inulin group , the urinary lactulose recovery was significantly lower than the other 2 groups . There were no significant differences in urinary mannitol levels between groups . Accordingly , the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups . The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups . The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2 , suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders BACKGROUND Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery , there are no reports of the effect on elective living-donor liver transplantation ( LDLT ) . METHODS Fifty adult patients undergoing LDLT between September 2005 and June 2009 were r and omized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy ( Bifidobacterium breve , Lactobacillus casei , and galactooligosaccharides [ the BLO group ] ) and a group without synbiotic therapy ( the control group ) . Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group . RESULTS Only 1 systemic infection occurred in the BLO group ( 4 % ) , whereas the control group showed 6 infectious complications ( 24 % ) , with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp ( P = .033 vs BLO group ) . No other type of complication showed any difference between the groups . CONCLUSIONS Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy OBJECTIVE Enteral administration of synbiotics has been reported to be beneficial during various types of surgery , but its clinical value in elderly surgical patients remains unclear . The aim of this study was to quantitatively evaluate the changes in gut microbiota and environment induced by perioperative synbiotic therapy , and to investigate whether it is possible to reduce infectious complications in elderly patients undergoing gastroenterological surgery . METHODS Forty-eight patients over the age of 70 y were r and omized into a group receiving 7 d of preoperative and 10 d of postoperative synbiotic therapy ( S group ) and a control group without synbiotic therapy ( C group ) . A fecal sample collected before and after surgery in each group was used for a quantitative evaluation of the microbiota . RESULTS Forty-eight patients completed the trial ( 25 in the S group and 23 in the C group ) . Synbiotic therapy significantly maintained the status of Bifidobacterium and Lactobacillus , whereas the number of Enterobacteriaceae , Staphylococcus , and Pseudomonas was significantly decreased . The total organic acid and short-chain fatty acid concentrations were increased , and the pH was markedly decreased , in the S group compared with the C group . The incidence of postoperative infectious complications was 12 % in the S group and 36 % in the C group , however , the difference did not reach statistical significance ( P = 0.06 ) . A multivariate analysis revealed that only the use of perioperative blood transfusion was an independent risk factor for infectious complications . CONCLUSIONS Synbiotic therapy improved the intestinal microbial environment , and might decrease the incidence of infectious complications in elderly surgical patients This study was design ed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer ( CRC ) respective surgery . From November 2011 to September 2012 , a total of 60 patients diagnosed with CRC were r and omly assigned to receive probiotic ( n = 30 ) or placebo ( n = 30 ) treatment . The operative and post-operative clinical results including intestinal cleanliness , days to first - flatus , defecation , fluid diet , solid diet , duration of pyrexia , average heart rate , length of intraperitoneal drainage , length of antibiotic therapy , blood index changes , rate of infectious and non-infectious complications , postoperative hospital stay , and mortality were investigated . The patient demographics were not significantly different ( p > 0.05 ) between the probiotic treated and the placebo groups . The days to first flatus ( 3.63 versus 3.27 , p = 0.0274 ) and the days to first defecation ( 4.53 versus 3.87 , p = 0.0268 ) were significantly improved in the probiotic treated patients . The incidence of diarrhea was significantly lower ( p = 0.0352 ) in probiotics group ( 26.67 % , 8/30 ) compared to the placebo group ( 53.33 % , 16/30 ) . There were no statistical differences ( p > 0.05 ) in other infectious and non-infectious complication rates including wound infection , pneumonia , urinary tract infection , anastomotic leakage , and abdominal distension . In conclusion , for those patients undergoing confined CRC resection , perioperative probiotic administration significantly influenced the recovery of bowel function , and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia Summary BACKGROUND : Preoperative bowel cleaning for elective colorectal surgery is a routine procedure . Synbiotics ( probiotics plus prebiotics ) are known for their beneficial effects on gut immune function and maintenance of the gut barrier . The main purpose of this study was to replace preoperative mechanical bowel cleaning with synbiotics and to assess the systemic inflammatory response and clinical outcome in patients undergoing colorectal surgery . PATIENTS AND METHODS : A prospect i ve double-blind r and omized placebo-controlled trial was conducted in 68 patients . The first group of 20 patients received synbiotics , the second group of 28 patients prebiotics and heat-deactivated probiotics , and the third ( control ) group of 20 patients mechanical bowel cleaning prior to the operation . RESULTS : Significantly higher values of interleukin 6 ( IL-6 ) were detected 72 h after the operation in the synbiotic group ( P = 0.025 ) , as well as an increase of fibrinogen at 24 h postoperatively ( P = 0.030 ) . No statistical differences were found in leukocytes count , C-reactive protein or the lymphocyte/granulocyte ratio . There were no differences in postoperative complications between the groups . Mean hospital stay was 9.2 days in the prebiotic group , 9.5 days in the control group , and 10.95 days in the synbiotic group . CONCLUSIONS : Preoperative administration of prebiotics in elective colorectal surgery appears to have the same protective effect in preventing a postoperative inflammatory response as mechanical bowel cleaning . Further prospect i ve studies are needed to verify the effects of synbiotics Background . Early enteral nutrition with solutions containing prebiotics ( fiber ) and probiotics ( Lactobacillus ) is suggested to reduce bacterial translocation and minimize the incidence of infections after liver transplantation . Methods . In a prospect i ve , r and omized placebo-controlled trial consisting of 95 patients , we compared the incidence of postoperative infections and other complications after liver transplantation among three different groups , all supplied with early enteral nutrition : ( a ) st and ard formula plus selective bowel decontamination ( SBD ) , ( b ) fiber-containing formula plus living Lactobacillus plantarum 299 , and ( c ) fiber-containing formula plus heat-killed L plantarum 299 . Results . The groups were comparable regarding preoperative American Society of Anesthesiologists classification , Child-Pugh classification of cirrhosis , operative data , and degree of immunosuppression . The patients who received living lactobacilli plus fiber developed significantly fewer bacterial infections ( 13 % ) than the patients with SBD ( 48 % ) . The incidence of infections was 34 % in the group with inactivated lactobacilli and fiber . Cholangitis and pneumonia were the leading infections and enterococci the most commonly isolated bacteria . In the living Lactobacillus group , the mean duration of antibiotic therapy , the mean total hospital stay , and the stay on the intensive care unit were also shorter than in the groups with inactivated lactobacilli and fiber as well as with SBD . However , these differences did not reach statistical significance . Conclusions . Early enteral nutrition with fiber-containing solutions and living L plantarum 299 was well tolerated . It decreases markedly the rate of postoperative infections both in comparison with inactivated L plantarum 299 and significantly with SBD and a st and ard enteral nutrition formula . As it is a cheap and feasible alternative to SBD , further studies should evaluate whether this ecoimmunonutrition should be already started while patients are on the waiting list for transplantation BACKGROUND Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability . Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer . OBJECTIVE The objective was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery . DESIGN A total of 150 patients with colorectal carcinoma were r and omly assigned to the control group ( n = 75 ) , which received placebo , or the probiotics group ( n = 75 ) . Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively . Outcomes were measured by assessing bacterial translocation , postoperative intestinal permeability , serum zonulin concentrations , duration of postoperative pyrexia , and cumulative duration of antibiotic therapy . The postoperative infection rate , the positive rate of blood microbial DNA , and the incidence of postoperative infectious complications-including septicemia , central line infection , pneumonia , urinary tract infection , and diarrhea-were also assessed . RESULTS The infection rate was lower in the probiotics group than in the control group ( P < 0.05 ) . Probiotics decreased the serum zonulin concentration ( P < 0.001 ) , duration of postoperative pyrexia , duration of antibiotic therapy , and rate of postoperative infectious complications ( all P < 0.05 ) . The p38 mitogen-activated protein kinase signaling pathway was inhibited by probiotics . CONCLUSIONS Perioperative probiotic treatment can reduce the rate of postoperative septicemia and is associated with reduced serum zonulin concentrations in patients undergoing colectomy . We propose a clinical regulatory model that might explain this association . This trial was registered at http://www.chictr.org/en/ as ChiCTR-TRC-00000423 AIM To investigate whether probiotic bacteria , given perioperatively , might adhere to the colonic mucosa , reduce concentration of pathogens in stools , and modulate the local immune function . METHODS A r and omized , double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer . Patients were allocated to receive either a placebo ( group A , n = 10 ) , or a dose of 10(7 ) of a mixture of Bifidobacterium longum ( BB536 ) and Lactobacillus johnsonii ( La1 ) ( group B , n = 11 ) , or the same mixture at a concentration of 10(9 ) ( group C , n = 10 ) . Probiotics , or a placebo , were given orally 2 doses/d for 3 d before operation . The same treatment continued postoperatively from day two to day four . Stools were collected before treatment , during surgery ( day 0 ) and 5 d after operation . During the operation , colonic mucosa sample s were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells ( DCs ) and lymphocyte subsets by surface antigen expression ( flow cytometry ) . The presence of BB536 and La1 was evaluated by the r and om amplified polymorphism DNA method with specific polymerase chain reaction probes . RESULTS The three groups were balanced for baseline and surgical parameters . BB536 was never found at any time-points studied . At day 0 , La1 was present in 6/10 ( 60 % ) patients in either stools or by biopsy in group C , in 3/11 ( 27.2 % ) in group B , and none in the placebo group ( P = 0.02 , C vs A ) . There was a linear correlation between dose given and number of adherent La1 ( P = 0.01 ) . The rate of mucosal colonization by enterobacteriacae was 30 % ( 3/10 ) in C , 81.8 % ( 9/11 ) in B and 70 % ( 7/10 ) in A ( P = 0.03 , C vs B ) . The Enterobacteriacae count in stools was 2.4 ( log10 scale ) in C , 4.6 in B , and 4.5 in A ( P = 0.07 , C vs A and B ) . The same trend was observed for colonizing enterococci . La1 was not found at day + 5 . We observed greater expression of CD3 , CD4 , CD8 , and naive and memory lymphocyte subsets in group C than in group A with a dose response trend ( C > B > A ) . Treatment did not affect DC phenotype or activation , but after ex vivo stimulation with lipopolysaccharides , groups C and B had a lower proliferation rate compared to group A ( P = 0.04 ) . Moreover , dendritic phenotypes CD83 - 123 , CD83-HLADR , and CD83 - 11c ( markers of activation ) were significantly less expressed in patients colonized with La1 ( P = 0.03 vs not colonized ) . CONCLUSION La1 , but not BB536 , adheres to the colonic mucosa , and affects intestinal microbiota by reducing the concentration of pathogens and modulates local immunity BACKGROUND We have already reported that , for patients undergoing elective colon cancer operations , perioperative infection can be prevented by a single intravenous dose of an antibiotic given immediately beforeh and if mechanical bowel preparation and the administration of oral antibiotics are implemented . Synbiotics has been reported to reduce the rate of infection in patients after pancreatic cancer operations . The effectiveness of oral antibiotics and probiotics in preventing postoperative infection in elective colon cancer procedures was examined in a r and omized controlled trial . METHODS Three hundred ten patients with colon cancer r and omly were assigned to one of three groups . All patients underwent mechanical bowel preparation and received a single intravenous dose of flomoxef immediately before operation . Probiotics were administered in Group A ; oral antibiotics were administered in Group B ; and neither probiotics nor oral antibiotics were administered in Group C. Stool sample s were collected 9 and 2 days before and 7 and 14 days after the procedure . Clostridium difficile toxin and the number of bacteria in the intestine were determined . RESULTS The rates of incisional surgical-site infection were 18.0 % , 6.1 % , and 17.9 % in Groups A , B , and C , and the rates of leakage were 12.0 % , 1.0 % , and 7.4 % in Groups A , B , and C , respectively , indicating that both rates were lesser in Group B than in Groups A and C ( P = .014 and P = .004 , respectively ) . The detection rates of C. difficile toxin were not changed among the three groups . CONCLUSION We recommend oral antibiotics , rather than probiotics , as bowel preparation for elective colon cancer procedures to prevent surgical-site infections Summary Background Data : Use of synbiotics has been reported to benefit human health , but clinical value in surgical patients remains unclear . Objective : To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function , immune responses , systemic inflammatory responses , microflora , and surgical outcome in patients undergoing high-risk hepatobiliary resection . Methods : Patients with biliary cancer involving the hepatic hilus ( n = 101 ) were r and omized before hepatectomy , into a group receiving postoperative enteral feeding with synbiotics ( group A ) ; or another receiving preoperative plus postoperative synbiotics ( group B ) . Lactulose-mannitol ( L/M ) ratio , serum diamine oxidase ( DAO ) activity , natural killer ( NK ) cell activity , interleukin-6 ( IL-6 ) , fecal microflora , and fecal organic acid concentrations were determined before and after hepatectomy . Postoperative infectious complications were recorded . Results : Of 101 patients , 81 completed the trial . Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups . Preoperatively in group B , NK activity , and lymphocyte counts increased , while IL-6 decreased significantly ( P < 0.05 ) . Postoperative serum IL-6 , white blood cell counts , and C-reactive protein in group B were significantly lower than in group A ( P < 0.05 ) . During the preoperative period , numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B ( P < 0.05 ) . Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A ( P < 0.05 ) . Incidence of postoperative infectious complications was 30.0 % ( 12 of 40 ) in group A and 12.1 % ( 5 of 41 ) in group B ( P < 0.05 ) . Conclusions : Preoperative oral administration of synbiotics can enhance immune responses , attenuate systemic postoperative inflammatory responses , and improve intestinal microbial environment . These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer |
420 | 22,336,794 | There was insufficient evidence to determine whether one type of removable dental prosthesis ( RDP ) was better or worse than another .
With fixed dental prostheses ( FDPs ) , there was no evidence that high gold alloys are better or worse than other alloys , nor that gold alloys or frameworks are better or worse than titanium .
There is insufficient evidence to determine whether zirconia is better or worse that other FDP material s , that ceramic abutments are better or worse than titanium , or that one cement was better or worse than another in retaining FDPs .
Based on trials meeting the inclusion criteria for this review , there is insufficient evidence to recommend a particular method of tooth replacement for partially edentulous patients | BACKGROUND Management of individuals presenting with partial loss of teeth is a common task for dentists .
Outcomes important to the management of missing teeth in the partially absent dentition should be systematic ally summarized .
This review recognizes both the challenges associated with such a summarization and the critical nature of the information for patients .
OBJECTIVES To assess the effects of different prostheses for the treatment of partially absent dentition in terms of the following outcomes : long-term success , function , morbidity and patient satisfaction . | OBJECTIVES A clinical trial , involving 203 resin-bonded bridges ( RBBs ) was undertaken to investigate the influence of retainer-type and luting material on the survival of these restorations . METHODS For this evaluation , 157 patients were available ( 14 % of the original sample was lost to follow-up or excluded from the study following the stopping criteria ) . Fifty per cent of the patients were question ed concerning the fate of the RBBs and 59 % of question ed patients were examined clinical ly . The patients that were seen for examination were representatives of the experimental groups . The findings from the clinical examination were compared with the data obtained from the question naire . Missing data were censored at the date of the last available information . Kaplan-Meier estimates were calculated to assess the survivals at the endpoints and compared using Cox 's proportional hazards procedure . RESULTS A significant difference was found between perforated ( P-type ) and etched ( E-type ) RBBs ( P = 0.05 ) for original bonded restorations but not when rebonded RBBs were taken into account . The results of the survival analysis were : anterior P-type , 49 + /- 7 % after 10.5 years : anterior E-type , 57 + /- 7 % after 10.5 years ; posterior P-type , 18 + /- 11 % after 6.8 years ; posterior E-type , 37 + /- 13 % after 10.2 years . Survivals of RBBs that were rebonded once during the evaluation period were 62 + /- 9 % ( 11.0 years ) for anterior RBBs and 51 + /- 11 % ( 10.2 years ) for posterior RBBs . CONCLUSIONS The factor location ( anterior versus posterior ) was as in previous analyses , highly significant . Differences in survival between cementation material s were not significant OBJECTIVES The aim of the present study was to evaluate the outcome of immediate functional loading of implants in single-tooth replacement using two different installation procedures . MATERIAL AND METHODS One hundred and fifty-one subjects , who required single-tooth rehabilitation in the area of 15 - 25 and 35 - 45 , were enrolled in eight private clinics in Italy . The implant sites were r and omly allocated to one of the following treatment groups . In the control group , in which a st and ard preparation procedure for implant placement and submerged healing of the implant was used , abutment connection and loading of the implants were performed 3 months after installation . In the test group 1 , a st and ard preparation procedure for the implant placement and immediate functional loading of implant was carried out . In the test 2 group , however , a modified implant installation procedure ( osteotome technique ) was used followed by immediate functional loading of the implant . Clinical and radiographic examinations were performed at 3 and 12 months of follow-up at all sites . RESULTS Three implants ( 5.5 % ) from the test 2 group ( osteotome preparation ) and one ( 2 % ) from the test 1 group ( conventional drill preparation ) failed to integrate and were removed one and three months after implant installation . The mean marginal bone loss assessed at 12 months was 0.31 mm ( test 1 ) , 0.25 mm ( test 2 ) and 0.38 mm ( control ) ( no statistically significant differences were found between the three treatment groups . ) CONCLUSION It is suggested that immediate functional loading of implants that are placed with a conventional installation technique and with sufficient primary stability may be considered as a valid treatment alternative in a single-tooth replacement Background Various treatment options for the prosthetic treatment of jaws where all molars are lost are under discussion . Besides the placement of implants , two main treatment types can be distinguished : replacement of the missing molars with removable dental prostheses and non-replacement of the molars , i.e. preservation of the shortened dental arch . Evidence is lacking regarding the long-term outcome and the clinical performance of these approaches . High treatment costs and the long time required for the treatment impede respective clinical trials . Methods / design This 14-center r and omized controlled investigator-initiated trial is ongoing . Last patient out will be in 2010 . Patients over 35 years of age with all molars missing in one jaw and with at least both canines and one premolar left on each side were eligible . One group received a treatment with removable dental prostheses for molar replacement ( treatment A ) . The other group received a treatment limited to the replacement of all missing anterior and premolar teeth using fixed bridges ( treatment B ) . A pilot trial with 32 patients was carried out . Two hundred and fifteen patients were enrolled in the main trial where 109 patients were r and omized for treatment A and 106 for treatment B. The primary outcome measure is further tooth loss during the 5-year follow-up . The secondary outcome measures encompassed clinical , technical and subjective variables . The study is funded by the Deutsche Forschungsgemeinschaft ( German Research Foundation , DFG WA 831/2 - 1 , 2 - 2 , 2 - 3 , 2 - 4 , 2 - 5 ) . Discussion The particular value of this trial is the adaptation of common design components to the very specific features of complex dental prosthetic treatments . The pilot trial proved to be indispensable because it led to a number of adjustments in the study protocol that considerably improved the practicability . The expected results are of high clinical relevance and will show the efficacy of two common treatment approaches in terms of oral health . An array of secondary outcome measures will deliver valuable supplementary information . If the results can be implemented in the clinical practice , the daily dental care should strongly profit thereof . Trial registration The trial is registered at Clinical Trials.gov under IS RCT N68590603 ( pilot trial ) and IS RCT N97265367 ( main trial ) PURPOSE This is a 2-year report from an ongoing prospect i ve 5-year multicenter study . The aim of the study was to evaluate the short- and long-term clinical function of CerAdapt ceramic abutments supporting short-span fixed partial dentures ( FPD ) . MATERIAL S AND METHODS Initially , 105 Brånemark System implants were placed in a total of 32 patients at 3 different clinics . After initial healing 103 implants remained . For the support of 36 FPDs , 53 ceramic and 50 titanium abutments were connected , 19 on ceramic and 17 on titanium abutments . RESULTS All patients remained in the study after 2 years . There was a cumulative survival rate of 97.1 % for implants and a cumulative success rate of 97.2 % for FPDs ( 94.7 % for ceramic and 100 % for titanium abutment-supported FPDs ) . One of 53 ceramic but none of 50 titanium abutments failed , giving a cumulative success rate of 98.1 % and 100 % , respectively , for the abutments . Soft tissue around abutments and adjacent teeth appeared healthy . More crown margins were placed submucosally at titanium ( 31 % ) than at ceramic ( 14 % ) abutments , and the level of the periimplant mucosa was relatively stable in relation to the abutment/crown . No differences were seen between ceramic and titanium abutments regarding bleeding of the periimplant mucosa . There was a minimal marginal bone loss recorded after 1 year , which was slightly more at titanium ( 0.4 mm ) than at ceramic ( 0.2 mm ) abutments . All patients and dentists were satisfied with the achieved esthetic result and no FPD was remade because of compromised esthetics . CONCLUSION So far the ceramic abutments have worked very well and the 2-year results have been very encouraging for CerAdapt abutments supporting short-span FPDs . However , ceramic material s tend to undergo static fatigue , and it is therefore important to wait for the 5-year results before making any more definite statement about the long-term prognosis for CerAdapt abutments A r and omized clinical trial was undertaken to compare the effectiveness of two partial denture design s , one with I-bar ( bar ) and the other with circumferential retainers ( circumferential ) , in 134 patients with Kennedy class I and class II edentulous conditions . A total of 30 partial dentures were considered failures , five because of abutment failures and 25 because of the lack of removable partial denture use for eating . The 5-year success rate of 71.3 % for the circumferential design did not differ significantly from the 76.6 % for the bar design ( p > 0.05 ) . There were no discernible changes in the nine periodontal health components of abutment teeth with either of the two design s after 60 months . The results indicate that the two design s do not differ significantly in terms of success rates , maintenance care , and effects on abutment teeth . A well-constructed removable partial denture of either design , supported by favorable abutments and accompanied by a regular recall program offers a satisfactory treatment modality AIM The aim of this research was to evaluate patients ' preferences for resin analogs of four major connector design s formulated to have equal rigidity once fabricated in the same alloy . METHODS AND MATERIAL S Nineteen Kennedy Class I or II partially edentulous patients participated at two centers . The four major connector analogs ( MCAs ) were fabricated for each subject using light-polymerizing acrylic resin . The subjects were asked to wear each of them in the mouth for 30 seconds in six pairs in r and om order , and to report their preference for each pair . Based on these data , the four analogs were ranked in a descending preference order for each patient . Within-subject comparisons preferences were performed with the Friedman test , and the multiple comparisons were performed with the Wilcoxon Signed Ranks test for data of each sample independently . RESULTS Statistically significant and consistent preference orders were revealed for both sample s , and the thin and wide design was significantly preferred to the thick and narrow design . However , a higher variation was observed for the first preference of each subject . CONCLUSIONS Subjects demonstrated a tendency to prefer thinner MCAs . However , the individual predilections of patients may not be an appropriate basis for an attempt to find a ' best design ' applicable to all patients Pulpal injury commonly occurs with tooth preparation for complete fixed partial dentures . This can be documented by the substantial incidence of pain after tooth preparation . In this study , a 4 % potassium nitrate-zinc oxide eugenol temporary cement was used to secure provisional crowns over recently prepared teeth and it significantly reduced the incidence and severity of pain after tooth preparation and impression taking PURPOSE The aim of this study was to evaluate the short-term bone level response around immediately placed and provisionally restored implants using a platform switching concept . MATERIAL S AND METHODS Twenty-two implants with a platform diameter of 5.5 mm were immediately placed in healthy maxillary sites in 22 patients . Result ant circumimplant spaces were filled with a mixture of bovine bone matrix and collagen . The implants were r and omly divided into two equal groups : 11 implants connected with 3.8-mm-diameter abutments ( test group ) and 11 with 5.5-mm-diameter ones ( control ) . Provisional crowns were adapted and adjusted for nonfunctional immediate placement on each implant and the final crowns were constructed 2 months later . Posttreatment assessment s were carried out by an independent trained observer at the time of implant placement ( baseline ) , at definitive prosthesis insertion , and every 6 months thereafter . These assessment s included periapical radiographs , pocket probing depths ( PPD ) , bleeding on probing ( BOP ) , and modified Plaque Index ( mPII ) on both implants and first proximal teeth . An image analysis software application was used to compare the bone crestal heights at the mesial and distal aspects of the implants . RESULTS The mean follow-up observation period was 25 months and all implants were judged to be successfully osseointegrated . In the test group , radiographic analysis showed an average bone reduction level of 0.30 mm ( SD = 0.16 mm ) . This mean value was statistically significantly different ( P < or = .005 ) from the average reduction in the control group ( mean = 1.19 mm , SD = 0.35 mm ) . No differences between the two groups in PPD , BOP , or mPII were found . CONCLUSION This preliminary study suggests that immediate single implant restorations in specific maxillary sites with subsequent platform switching may provide peri-implant alveolar bone-level stability The clinical question at issue , whether it is possible to combine implants and natural teeth via fixed bridges , is of current interest . The treatment of the subjects of this prospect i ve study was performed between June 1984 and December 1986 . This article presents the 5-year results of the study . The consecutive patient material comprised 23 patients with Applegate Kennedy Class I residual dentition in the m and ible and a complete maxillary denture . All 23 patients were provided with implants ad modum Brånemark in each m and ibular quadrant . One side was r and omized to rehabilitation with fixed bridge between the distal tooth of the residual dentition and an implant ; the other side received a free-st and ang bridge on 2 implants . The fixture survival rate was 88 % . No difference was found between the two sides . Bridge stability was 89 % for the implant bridges and 91 % for the combination bridges . The change in marginal bone level at the implants was small during the 5-year follow up period ( on average 0.1 - 0.3 mm ) and with no difference between the two sides . In conclusion , it was not possible to demonstrate any higher risk of implant or prosthetic failure for tooth-implant fixed bridges compared with implant-supported bridges OBJECTIVES The aim was to test whether or not zirconia abutments exhibit the same survival and technical/biological outcome as titanium abutments . MATERIAL AND METHODS Twenty-two patients receiving 40 single-tooth implants in canine and posterior regions were included . The implant sites were r and omly assigned to 20 zirconia and 20 titanium abutments . All-ceramic and metal-ceramic crowns were fabricated . At baseline , 6 , 12 and 36 months , the reconstructions were examined for technical and biological problems . Probing pocket depth ( PPD ) , plaque control record ( PCR ) and bleeding on probing ( BOP ) were assessed at abutments ( test ) and analogous contralateral teeth ( control ) . St and ardized radiographs of the implants were made and the bone level ( BL ) was measured referring to the implant shoulder on mesial ( mBL ) and distal sides ( dBL ) . The difference of color ( DeltaE ) of the peri-implant mucosa and the gingiva of control teeth was assessed with a spectrophotometer . The data were statistically analyzed with Mann-Whitney Rank and Student 's unpaired t-tests . RESULTS Eighteen patients with 18 zirconia and 10 titanium abutments were examined at a mean follow-up of 36 months ( range 31.5 - 53.3 months ) . No fracture of an abutment or loss of a reconstruction was found . Hence , both exhibited 100 % survival . At two metal-ceramic crowns supported by titanium abutments chipping of the veneering ceramic occurred . No difference of the biological outcome of zirconia and titanium abutments was observed : PPD ( meanPPD(ZrO(2 ) ) 3.2 + /- 1 mm , mPPD(Ti ) 3.4 + /- 0.5 mm ) , PCR ( mPCR(ZrO(2 ) ) 0.1 + /- 0.2 , mPCR(Ti ) 0.1 + /- 0.2 ) and BOP ( mBOP(ZrO(2 ) ) 0.4 + /- 0.4 , mBOP(Ti ) 0.2 + /- 0.3 ) . Furthermore , the BL was similar at implants supporting zirconia and titanium abutments ( mBL(ZrO(2 ) ) 1.7 + /- 1 , dBL(ZrO(2 ) ) 1.6 + /- 1 ; mBL(Ti ) 2 + /- 1 , dBL(Ti ) 2.1 + /- 1 ) . Both , zirconia and titanium abutments induced a similar amount of discoloration of the mucosa compared with the gingiva at natural teeth ( DeltaE(ZrO(2 ) ) 9.3 + /- 3.8 , DeltaE(Ti ) 6.8 + /- 3.8 ) . CONCLUSIONS At 3 years , zirconia and titanium abutments exhibited same survival and technical , biological and esthetical outcomes The aim of this r and omized controlled clinical trial was to compare the early clinical outcome of slip-cast glass-infiltrated Alumina/Zirconia and CAD/CAM Zirconia all-ceramic crowns . A total of 30 InCeram ® Zirconia and Cercon ® Zirconia crowns were fabricated and cemented with a glass ionomer cement in 20 patients . At baseline , 6-month , 1-year , and 2-year recall appointments , Californian Dental Association ( CDA ) quality evaluation system was used to evaluate the prosthetic replacements , and plaque and gingival index scores were used to explore the periodontal outcome of the treatments . No clinical sign of marginal discoloration , persistent pain and secondary caries was detected in any of the restorations . All InCeram ® Zirconia crowns survived during the 2-year period , although one nonvital tooth experienced root fracture coupled with the fracture of the veneering porcelain of the restoration . One Cercon ® Zirconia restoration fractured and was replaced . According to the CDA criteria , marginal integrity was rated excellent for InCeram ® Zirconia ( 73 % ) and Cercon ® Zirconia ( 80 % ) restorations , respectively . Slight color mismatch rate was higher for InCeram ® Zirconia restorations ( 66 % ) than Cercon ® Zirconia ( 26 % ) restorations . Plaque and gingival index scores were mostly zero and almost constant over time . Time-dependent changes in plaque and gingival index scores within and between groups were statistically similar ( p>0.05 ) . This clinical study demonstrates that single-tooth InCeram ® Zirconia and Cercon ® Zirconia crowns have comparable early clinical outcome , both seem as acceptable treatment modalities , and most importantly , all-ceramic alumina crowns strengthened by 25 % zirconia can sufficiently withst and functional load in the posterior zone The roughness of intraoral hard surfaces plays an important role in bacterial adhesion and colonization . Earlier studies have shown that rough surfaces accumulate up to 25 times more subgingival plaque than do smooth sites . In the present study , the influence of surface smoothing was studied . In six partially edentulous patients waiting for a fixed prosthesis supported by endosseous titanium implants , four titanium abutments with different surface roughness were r and omly placed . After 1 month of intraoral exposure , subgingival plaque sample s from each abutment were compared within each patient by means of differential phase-contrast microscopy . After 3 months , supragingival and subgingival plaque sample s were taken from all abutments for differential phase-contrast microscopy and culturing . Probing depth , recession , and bleeding upon probing were scored at the same visit . Differential phase-contrast microscopy showed that subgingivally , only the two roughest abutments harbored spirochetes after 1 month . After 3 months , subgingivally , the composition of the flora showed little variation on the different abutment types , although spirochetes were only noticed around the roughest abutments . Anaerobic culturing result ed in comparable amounts of colony-forming units for all abutment types , both supragingivally and subgingivally . Subgingivally , the microbiologic composition did not show major interabutment differences . Clinical ly , small differences in probing depth were observed . The roughest abutment showed some attachment gain ( 0.2 mm ) during 3 months , whereas all other abutments had an attachment loss ranging from 0.8 to greater than 1 mm . The results indicate that a reduction in surface roughness ( less than a roughness of 0.2 micron ) had no major effect on the microbiologic composition , supragingivally or subgingivally . These observations indicate the existence of a threshold roughness below which no further impact on the bacterial adhesion and /or colonization should be expected . However , clinical evaluation seems to indicate that a certain surface roughness is necessary for increased resistance to clinical probing PURPOSE A prospect i ve , r and omized , controlled 5-year multicenter study evaluated the long-term clinical function of CerAdapt ceramic abutments compared to titanium abutments on Brånemark implants supporting short-span fixed partial dentures ( FPD ) . MATERIAL S AND METHODS Initially , 105 Brånemark implants were placed in a total of 32 patients at three different clinics ; 103 implants remained after initial healing . Fifty-three ceramic and 50 titanium abutments were connected to support 36 FPDs , 19 on ceramic and 17 on titanium abutments . RESULTS Thirty patients with 29 FPDs were examined after 5 years . There was a cumulative success rate of 97.2 % for FPDs ( 94.7 % for ceramic and 100 % for titanium abutment-supported FPDs ) . One of 53 ceramic and none of 50 titanium abutments failed , giving survival rates of 98.1 % and 100 % , respectively . There was a mean marginal bone loss of 0.3 mm and 0.4 mm , respectively , for ceramic and titanium abutments . Soft tissues around abutments and adjacent teeth appeared healthy , and no significant differences were recorded for mucosal bleeding and plaque between ceramic and titanium abutments . Crown margins at FPD insertion were positioned as follows : 21 % submucosally , 33 % at the mucosal margin , and 46 % supramucosally . Changes in mucosal level were recorded at 12 % of the abutments , with 73 % of all changes recorded at ceramic abutments . There was a balance between more or less exposed crown margins during the first 2 years , in contrast to the 2- to 5-year period , when all changes meant less exposed margins . CONCLUSION Safe long-term functional and esthetic results can be achieved with CerAdapt alumina ceramic abutments on Brånemark implants for short-span FPDs Bacterial adhesion to intra-oral , hard surfaces is firmly influenced by the surface roughness to these structures . Previous studies showed a remarkable higher subgingival bacterial load on rough surfaces when compared to smooth sites . More recently , the additional effect of a further smoothening of intra-oral hard surfaces on clinical and microbiological parameters was examined in a short-term experiment . The results indicated that a reduction in surface roughness below R(a ) = 0.2 microns , the so-called " thresholds R(a ) " , had no further effect on the quantitative/qualitative microbiological adhesion or colonisation , neither supra- nor subgingivally . This study aims to examine the long-term effects of smoothening intra-oral hard transgingival surfaces . In 6 patients expecting an overdenture in the lower jaw , supported by endosseus titanium implants , 2 different abutments ( transmucosal part of the implant ) : a st and ard machined titanium ( R(a ) = 0.2 microns ) and one highly polished and made of a ceramic material ( R(a ) = 0.06 microns ) were r and omly installed . After 3 months of intra-oral exposure , supra- and subgingival plaque sample s from both abutments were compared with each other by means of differential phase-contrast microscopy ( DPCM ) . Clinical periodontal parameters ( probing depth , gingival recession , bleeding upon probing and Periotest-value ) were recorded around each abutment . After 12 months , the supra- and subgingival sample s were additionally cultured in aerobic , CO2-enriched and anaerobic conditions . The same clinical parameters as at the 3-month interval were recorded after 12 months . At 3 months , spirochetes and motile organisms were only detected subgingivally around the titanium abutments . After 12 months , however , both abutment-types harboured equal proportions of spirochetes and motile organisms , both supra- and subgingivally . The microbial culturing ( month 12 ) failed to detect large inter-abutment differences . The differences in number of colony- forming units ( aerobic and anaerobic ) were within one division of a logarithmic scale . The aerobic culture data showed a higher proportion of Gram-negative organisms in the subgingival flora of the rougher abutments . From the group of potentially " pathogenic " bacteria , only Prevotella intermedia and Fusobacterium nucleatum were detected for anaerobic culturing and again the inter-abutment differences were negligible . Clinical ly , the smoothest abutment showed a slightly higher increase in probing depth between months 3 and 12 , and more bleeding on probing . The present results confirm the findings of our previous short-term study , indicating that a further reduction of the surface roughness , below a certain " threshold R(a ) " ( 0.2 microns ) , has no major impact on the supra- and subgingival microbial composition PURPOSE Removable partial dentures ( RPD ) used to restore the severely shortened m and ible may adversely affect the remaining natural teeth and are associated with a low prevalence of use . This pilot study investigated patient satisfaction following restoration of m and ibular shortened dental arches . MATERIAL S AND METHODS Sixty subjects with m and ibular shortened dental arches entered a r and omized controlled trial comparing two types of m and ibular prostheses : bilateral free-end saddle RPDs and distal cantilever resin-bonded fixed partial dentures ( FPD ) . Patient satisfaction was assessed using self-administered question naires before ( baseline ) , 3 months after , and 1 year after provision of new prostheses . RESULTS Improvements in levels of general satisfaction with teeth , appearance of teeth , and perceived masticatory ability were significant for the FPD group . Significant improvements in perceived masticatory ability were noted for both groups . There were also significant improvements in perceived levels of comfort of m and ibular prostheses in both groups . Changes in summary satisfaction scores indicated improved satisfaction for both treatment groups but suggested a larger clinical effect for the FPD group . Significant differences between treatment groups were not established . CONCLUSION Patient-based outcomes reported suggested that resin-bonded cantilever FPDs are an effective means of restoring the shortened m and ibular dental arch in terms of patient comfort and acceptance A multi-centre r and omized clinical trial is under way at 14 university dental schools in Germany to compare prosthodontic treatments for the shortened dental arch ( SDA ) . One of the aims of this pilot- study was to measure the effect of two treatment options of the SDA on oral health-related quality of life and on the Research Diagnostic Criteria ( RDC ) for temporom and ibular disorders ( TMD ) . Thirty-four patients participated in the pilot- study . Inclusion criteria were : all molars were missing and the presence of at least both canines and one premolar in each quadrant . Participants were r and omly assigned to receive either removable partial dentures including molar replacement ( RPD_group ) or retain a premolar occlusion ( PROC_group ) . The Oral Health Impact Profile ( OHIP-49 ) and the RDC for TMD were completed by participants before treatment ( pre-treatment ) , 6 weeks ( 6 wks ) , 6 months ( 6 m ) and 12 months ( 12 m ) after treatment . At the 12-month follow up , data of 10 women and 11 men ( mean age : 62 + /- 10 years ) were available . Medians of the OHIP total-scores were as follows : RPD ( n = 10 ) , 43.5 ( pre-treatment ) , 18.2 ( 6 wks ) , 13.3 ( 6 m ) , 14.7 ( 12 m ) . PROC ( n = 11 ) : 31.8 ( pre-treatment ) , 27.1 ( 6 wks ) , 8.8 ( 6 m ) , 8.3 ( 12 m ) . Significant differences were shown for RPD_group between pre-treatment and 6m/12 m and for PROC_group between pre-treatment and 6 m . There were no significant differences between treatment groups at any time . Within each group , an improvement of life- quality was observed . No significant difference could be reported between the two therapy concepts . This may be due to the low sample size within the pilot study The aim of this r and omized controlled clinical trial was to evaluate over a 5-year period , the clinical outcome of shrinkage-free ZrSiO(4)-ceramic ( KaVo Everest HPC ) full coverage crowns on posterior teeth in comparison with conventional gold crowns that served as the control . This study reports results of a 5-year study protocol up to 24 months . Patients totalling 224 were r and omly divided into two treatment groups . Of these , 123 patients were restored with 123 Everest HPC crowns , fabricated by the Kavo Everest computer-aided manufacturing ( CAM ) procedure and 101 patients received 101 gold crowns , but two were excluded from analysis . All crowns were conventionally cemented with glass-ionomer cement . After an observation period of 6 , 12 and 24 months , the prospect i ve survival rates ( Kaplan-Meier ) for the KaVo Everest HPC crowns were 97.9 % , 95.1 % and 89.8 % and for the gold crowns 100 % , 94.8 % and 92.7 % , respectively . There were no significant differences between the two groups ( P = 0.2 ) . The 1-year failure rates were 4.9 % for the KaVo Everest HPC crowns and 5.2 % for the gold crowns . The 1-year cumulative risks for loss of vitality , secondary caries , fractures , loss of crown and extraction of abutment of the analyzed abutments ( 88 ) were 8.9 % , 0 % , 0 % , 1.1 % and 1.1 % , respectively , for the gold crowns and 2.8 % , 0 % , 4.7 % , 0 % and 0.9 % , respectively , for the ceramic crowns ( 107 analyzed abutments ) . No perfect marginal fit was shown by 49.5 % of the evaluated ceramic crowns and 26.1 % of the gold crowns . Only 1.9 % of the KaVo Everest HPC crowns had a marginal crevice . In conclusion , Everest HPC crowns with an adequate occlusal tooth reduction of > 1.5 mm are suitable for posterior restorations , but the marginal fit shows a potential for improvement PURPOSE The purpose of this prospect i ve clinical study was to compare titanium and gold-alloy abutments when used with cemented , implant-supported single-tooth crowns . For 4 years following prosthodontic rehabilitation , these abutments were evaluated with respect to peri-implant marginal bone levels and peri-implant soft tissue parameters . MATERIAL S AND METHODS During the years 1998 to 2000 , 20 patients were selected from a patient population receiving treatment in the Implantology Department at the University of Padova , Italy . They all presented with single-tooth bilateral edentulous sites in the premolar/molar region with adequate bone width , similar bone height on each side , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts on each side . Each subject received two identical implants ( one in each edentulous site ) . One was r and omly selected to be restored with a titanium abutment and a cemented implant-supported single-tooth crown , and the other was restored with a gold-alloy abutment and a cemented implant-supported single tooth crown . Data on peri-implant marginal bone levels and soft tissue parameters were collected for 4 years after abutment and crown insertion placement and analyzed to determine whether there was a significant ( p < .001 ) difference with respect to the type of abutments ( titanium vs. gold alloy ) used . RESULTS All subjects completed the study . All 40 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the two groups with respect to peri-implant marginal bone levels and soft tissue parameters . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different response with the peri-implant marginal bone and soft tissue when titanium or gold-alloy abutments were used in conjunction with the cemented , single-tooth implant restorations provided for this limited patient population . There was no evidence of different behavior of peri-implant marginal bone and of peri-implant soft tissue when titanium abutments or gold-alloy abutments were used for cemented single-tooth implant restorations in this limited patient population OBJECTIVES This r and omized-controlled trial aim ed to evaluate marginal bone level alterations at implants restored according to the platform-switching concept , using different implant/abutment mismatching . MATERIAL AND METHODS Eighty implants were divided according to the platform diameter in four groups : 3.8 mm ( control ) , 4.3 mm ( test group(1 ) ) , 4.8 mm ( test group(2 ) ) and 5.5 mm ( test group(3 ) ) , and r and omly placed in the posterior maxilla of 31 patients . After 3 months , implants were connected to a 3.8-mm-diameter abutment and final restorations were performed . Radiographic bone height was measured by two independent examiners at the time of implant placement ( baseline ) , and after 9 , 15 , 21 and 33 months . RESULTS After 21 months , all 80 implants were clinical ly osseointegrated in the 31 patients treated . A total of 69 implants were available for analysis , as 11 implants had to be excluded from the study due to early unintentional cover screw exposure . Radiographic evaluation showed a mean bone loss of 0.99 mm ( SD = 0.42 mm ) for test group(1 ) , 0.82 mm ( SD = 0.36 mm ) for test group(2 ) and 0.56 mm ( SD = 0.31 mm ) for test group(3 ) . These values were statistically significantly lower ( P<0.005 ) compared with control ( 1.49 mm , SD = 0.54 mm ) . After 33 months , five patients were lost to follow-up . Evaluation of the remaining 60 implants showed no difference compared with 21 months data except for test group(2 ) ( 0.87 mm ) and test group(3 ) ( 0.64 mm ) . There was an inverse correlation between the extent of mismatching and the amount of bone loss . CONCLUSIONS This study suggested that marginal bone level alterations could be related to the extent of implant/abutment mismatching . Marginal bone levels were better maintained at implants restored according to the platform-switching concept For the purpose of evaluating the clinical performance of 2 alternative dental casting alloys , 17 crowns made from the low-gold alloy Midas and 14 crowns made from the silver-palladium alloy Albacast were inserted at r and om into 23 patients . In each patient a high-gold type-3 alloy , JS C , served as a reference alloy . The patients were examined after 1 year with regard to tarnishing and certain factors such as plaque index , gingival index , and margin index . In addition , the California Dental Association 's quality evaluation of dental care was used by two independent calibrated examiners . The results of the present study showed that the crowns made of the silver-palladium alloy were tarnished and had rough occlusal surfaces more often than crowns made of the low-gold and high-gold alloys OBJECTIVES The literature demonstrates that conventional luting of metal-based restorations using zinc phosphate cements is clinical ly successful over 20 years . This study compared the clinical outcomes of metal-based fixed partial dentures luted conventionally with zinc phosphate and self-adhesive resin cement . METHODS Forty-nine patients ( mean age 54+/-13 years ) received 49 metal-based fixed partial dentures r and omly luted using zinc phosphate ( Richter & Hoffmann , Berlin , Germany ) or self-adhesive resin cement ( RelyX Unicem Aplicap , 3 M ESPE , Germany ) at the University Medical Center Regensburg . The core build-up material was highly viscous glass ionomer ; the finishing line was in dentin . The study included 42 posterior , 5 anterior crowns and two onlays . Forty-seven restorations were made of precious alloys , 2 of non-precious alloys . The restorations were clinical ly examined every year . The clinical performance was checked for plaque ( 0 - 5 ; PI , Quigley-Hein ) , bleeding ( 0 - 4 ; PBI ; Mühlemann ) and attachment scores . The examination included pulp vitality and percussion tests . STATISTICS Means of scores , st and ard deviation , cumulative survival and complication rates were calculated using life tables . RESULTS The mean observation time was 3.16+/-0.6 years ( min : 2.0 ; max : 4.5 years ) . During that time no restoration was lost , no recementation became necessary . One endodontic treatment was performed in the self-adhesive composite group after 2.9 years . At study end bleeding ( 1.44 RelyX Unicem vs. 1.25 zinc phosphate ) and plaque ( 1.64 RelyX Unicem vs. 1.0 zinc phosphate ) scores showed no statistically significant difference . SIGNIFICANCE The self-adhesive resin cement performed clinical ly as well and can be used as easily as zinc phosphate cement to retain metal-based restorations over a 38-month observation period PURPOSE The use of implants for prosthetic rehabilitation of partially edentulous patients is increasing . However , the possibilities of placing implants in the posterior part of the m and ible are often limited . The purpose of this longitudinal study with 10 years of follow-up was to evaluate the use of short implants supporting fixed partial dentures ( FPD ) in the posterior part of the m and ible , and to compare implant supported FPDs to tooth-implant supported FPDs . MATERIAL S AND METHODS The patient material comprised 23 patients with residual m and ibular anterior teeth , and each patient received FPDs unilaterally . On one side the FPD was supported by two implants , and on the other side by one implant and one tooth , thus permitting intraindividual comparison . The distribution of the two types of FPDs in each jaw was r and omized . Implant success rates , marginal bone changes , and mechanical complications were studied . RESULTS The tooth-implant connection did not demonstrate any negative influences on the overall success rates for the 10-year period , nor were the shorter implants found to be less favorable . CONCLUSION It is suggested that a prosthetic construction supported by both a tooth and an implant may be recommended as a predictable and reliable treatment alternative in the posterior m and ible A clinical trial of 201 posterior resin-bonded bridges ( PRBBs ) was conducted partially in a University clinic and partially in general dental practice s , for study of the influence of some experimental variables on the survival of these restorations . This report contains the results of an interim analysis which was done after 2.5 years ' follow-up . No significant differences were found among the bonding systems used to adhere the PRBBs ( Clearfil F2/etching , Panavia EX/s and blasting , and Microfill Pontic C/silicate-coating ) , or among the different preparation forms . PRBBs made in general dental practice s were as retentive as those made in the University clinic . The " location " factor was found to be highly significant ( p = 0.0001 ) . The survival rates were 81 % for maxillary PRBBs and 56 % for m and ibular PRBBs Removable partial dentures may adversely affect remaining tissues and have a low prevalence of use . This r and omized controlled trial was design ed to compare the time to survival of cantilever resin-bonded fixed partial dentures and conventional removable partial dentures to restore shortened lower dental arches . We r and omly allocated 25 male and 35 female patients ( median age , 67 years ) to fixed or removable partial denture groups of 30 persons , matched for age and sex . Survival of the prostheses was assessed , based on listed criteria , at each review or when problems arose . Although the removable partial denture group required rather more maintenance visits , the difference in survival rates was not statistically significant ( hazard ratio = 0.59 , with 95 % CI 0.27 , 1.29 ) . In the absence of significant differences in five-year survival , the reported advantages of fixed partial dentures , including reduced maintenance frequency , offer positive support for the use of resin-bonded fixed partial dentures PURPOSE The purpose of this prospect i ve multicenter study was to evaluate and compare the clinical performance of laser-welded titanium fixed partial implant-supported prostheses with conventional cast frameworks . MATERIAL S AND METHODS Forty-two partially edentulous patients were provided with Brånemark system implants and arranged into 2 groups . Group A was provided with a conventional cast framework with porcelain veneers in one side of the jaw and a laser-welded titanium framework with low-fusing porcelain on the other side . The patients in group B had an old implant prosthesis replaced by a titanium framework prosthesis . The patients were followed for 3 years after prosthesis placement . Clinical and radiographic data were collected and analyzed . RESULTS Only one implant was lost , and all prostheses were still in function after 3 years . The 2 framework design s showed similar clinical performance with few clinical complications . Only one abutment screw ( 1 % ) and 9 porcelain tooth units ( 5 % ) fractured . Four prostheses experienced loose gold screws ( 6 % ) . In group A , marginal bone loss was similar for both design s of prostheses , with a mean of 1.0 mm and 0.3 mm in the maxilla and m and ible , respectively . No bone loss was observed on average in group B. No significant relationship ( P > 0.05 ) was observed between marginal bone loss and placement of prosthesis margin or prosthesis design . CONCLUSION The use of laser-welded titanium frameworks seems to present similar clinical performance to conventional cast frameworks in partial implant situations after 3 years The aim of this study was to compare the prosthetic outcomes of implant/tooth-supported three-unit fixed partial dentures ( FPDs ) with those of freest and ing implant-supported FPDs after 2 years of function . Twenty-nine partially edentulous patients presenting with unilateral or bilateral distal-extension edentulous areas received FPDs and were followed for a minimum of 24 months . In all , 49 FPDs were fabricated . In 34 FPDs , implants were connected to teeth and thus the FPDs were categorized as mixed ( m-FPDs ) , whereas 15 FPDs were supported by freest and ing terminal implants ( fs-FPDs ) . Evaluation of prosthetic parameters including mechanical complications was performed . Changes in marginal bone level ( DeltaMBL ) around implants in both treatment groups were measured on digitalized periapical radiographs . Neither loss of osseointegration of an implant nor intrusion of abutment teeth was recorded . All FPDs were functioning after 24 months . Mean DeltaMBLs of posterior implants supporting m-FPDs and fs-FPDs at 24 months were 0.189 mm and -0.285 mm , respectively , representing a significant difference ( P < .05 ) . Mean DeltaMBLs at the mesial and distal surfaces of anterior and posterior implants supporting fs-FPDs were similar ( P > .05 ) . In the treatment of short-span distal-extension edentulous areas , similar clinical outcomes may be obtained for implant- and tooth/implant-supported three-unit FPDs in the early stages of function PURPOSE This study evaluated and compared the clinical performance of laser-welded titanium fixed partial implant-supported prostheses with that of conventional cast frameworks in the partially edentulous jaw . MATERIAL S AND METHODS Forty-two patients provided with Brånemark system implants were arranged into two groups . Twenty-one patients ( group A ) were provided with a conventional cast ceramometal framework in one side of the jaw and a laser-welded titanium framework with low-fusing porcelain in the other side . In group B , 21 patients received a titanium framework prosthesis to replace a conventional implant prosthesis . Clinical and radiographic data were collected for 5 years . RESULTS Four implants and one titanium framework were lost during the follow-up period . The two framework design s did not show any significant differences with regard to implant or prosthesis survival ( P > .05 ) . Few clinical complications were observed . In group A , marginal bone loss after 5 years was similar for both prosthesis design s , with an average of 0.1 mm and 0.3 mm in the maxilla and m and ible , respectively . Basically , no bone loss was observed on average in group B. Furthermore , no significant relationship was observed between marginal bone loss and placement of prosthesis margin or prosthesis design . CONCLUSION Except for an insignificant tendency toward a slightly higher incidence of small chips of porcelain veneers , laser-welded titanium frameworks presented an overall similar clinical performance as conventional cast frameworks in partial implant situations after 5 years This study was design ed to investigate and identify factors relevant to the success and failure of posterior resin-bonded bridges ( PRBBs ) related to the patient , technique , operator and bridge design . It was a long-term controlled clinical trial and formed part of a multicentered study on PRBBs . Data are presented 2.5 years from the start of the study . Following a strict protocol for case selection , 54 posterior , resin-bonded , fixed-fixed , three unit bridges were placed in 45 patients . Twenty-four patients with 27 PRBBs attended for 2.5-year recall . Treatment variables were limited to one of two operators and either a conventional tooth preparation or a more extensive modified preparation was performed . The allocation of treatment modalities was performed using a computer program to balance patient variables such as age , gender , location of bridge , restoration of abutment teeth . All bridges were produced in one laboratory , treated to produce a silicate-coating bond and placed using Microfill Pontic C ( Kulzer , Wehrheim , Germany ) . Data relating to the patients , the open spaces , bridge preparation , bridge placement and subsequent annual evaluation were recorded . The survival of PRBBs in the maxilla was 77 % and in the m and ible 47 % STATEMENT OF PROBLEM There is no known data on the functional efficacy of different removable partial denture design s. PURPOSE This r and omized clinical trial compared the masticatory performance of two commonly used design s in 118 patients who needed a unilateral or bilateral m and ibular partial denture . MATERIAL AND METHODS One half of the patients received a partial denture with distal occlusal rests and cast circumferential clasps and the other half a partial denture with mesial rests and I-bar cast clasps . The left side , right side , and swallowing threshold masticatory tests were made with peanuts and carrots before treatment and 16 weeks after the prosthesis insertion ( baseline ) and thereafter at 6 , 18 , 36 , and 60 months . RESULTS Masticatory scores at entry were higher in the circumferential design group , but the only significant ( p < 0.05 ) difference was found in the right side carrot performance . Both groups realized significant improvements ( p < 0.001 ) in all performance scores with partial dentures . Mean improvements of 24.7 with peanuts and 35.8 with carrots in the right side performance scores and 19.0 in the swallowing threshold score with peanuts in the bar design group were significantly higher ( p = 0.017 ) than the respective mean improvements of 15.9 , 21.4 , and 5.6 in the circumferential design group . However , no significant differences were found between the two groups for any of the 10 performance scores at baseline . CONCLUSIONS Despite some performance differences at entry , the mean performance scores for the two groups became similar at baseline and at subsequent intervals Five Veterans Administration centers have participated in a study to determine whether fixed partial dentures ( FPDs ) supported by blade implants offer an acceptable substitute for m and ibular unilateral or bilateral distal-base extension removable partial dentures ( RPDs ) . The study design and methodology have been described in Part I. A total of 232 patients received comprehensive dental care including RPDs for 118 patients and FPDs for 114 . Prespecified criteria determined treatment failures . During the 60-month period , treatment failures occurred in 19 FPD patients and 30 RPD patients . Ten FPD failures occurred before and nine after the FPD insertion . Five RPD failures were caused by abutment tooth loss and 25 for not using the RPD while eating . Life table analysis showed 5-year success rates of 84.2 % for the FPD and 74 % for the RPD . The 17.9 % higher FPD success rate in Kennedy class II patients was both statistically and clinical ly significant . Excluding the 10 early failures , the 5-year FPD success rate was 91.5 % . Of the 170 attempted implants , 26 failed , including 12 before the FPD fabrication . Radiographic assessment s by a panel of three judges showed no bone deterioration during baseline to 60 months in 29.6 % , slight in 25.4 % , moderate in 15.9 % , marked in 27 % , and severe deterioration in 2.1 % of the implant posts OBJECTIVE The immediate single-tooth implant has become a viable treatment option . However , the impact of the restorative procedure on esthetics is currently unclear . The goal of this study was to compare the soft tissue outline at immediate implants following two restorative protocol s : immediate connection of a temporary crown or submerged healing during which a removable partial denture is used . MATERIAL AND METHODS A 1-year single-blind r and omized clinical study was performed in 49 patients . Twenty-four patients were assigned to the immediate restoration group and 25 to the delayed restoration group . Clinical and radiographic evaluations of soft and hard tissues were carried out after 3 , 6 and 12 months . RESULTS Implant survival , bone remodeling , probing depth and bleeding tendency were not influenced by the restorative protocol . Delayed restoration result ed in initial papilla loss taking up to 1 year to attain comparable height as for immediate restoration . Midfacial recession was systematic ally 2.5 - 3 times higher following delayed restoration pointing to a 0.75 mm additional loss in comparison with immediate restoration after 1 year . CONCLUSIONS If the primary implant stability permits it , immediate single-tooth implants should be instantly provisionalized in the interest of optimal midfacial esthetics This study was conducted to determine whether fixed partial dentures supported by dental implants provide an acceptable alternative to conventional removable partial dentures in patients with Kennedy class I or class II edentulous conditions . The acceptability of the new treatment will be based on success rates , impact on the health of the remaining dentition , masticatory performance , patient satisfaction , and maintenance care and cost . The study was planned also to provide comparisons between two design s commonly used by dentists for fabricating removable partial dentures . The design s differed only in terms of the type of the retainer ( clasp type ) and tooth support ( rest location ) . A total of 272 patients with Kennedy class I and class II edentulous conditions were assigned on a r and om basis to one of the treatment groups , 134 to receive a removable partial denture and 138 a fixed partial denture supported by a blade-vent implant . All of the patients were medically screened and met prespecified criteria for oral hygiene , bone support for abutment teeth , and size of the residual ridge . Thirty-four patients were eliminated from the study before completion of their treatment . An additional six patients with early implant failures were reentered in the study and followed up as a separate group . The remaining 232 patients received comprehensive dental care , including removable partial dentures for 118 and fixed partial dentures for 114 patients . A series of examinations , radiographs , masticatory performance tests , patient satisfaction , food selection question naires , and dietary history were completed before initiation of the treatment , 16 weeks after the insertion of an RPD or an implant , and thereafter at 6- , 18- , 36- , and 60-month intervals . In addition , patients were seen at 6-month intervals for a recall dental examination , oral prophylaxis , plaque instructions , radiographic survey of the implant , and any needed dental treatment . The r and omization stratification approach produced two treatment groups with comparable age , number of remaining maxillary and m and ibular teeth , type of opposing dentition , and percent of patients with Kennedy class I and class II edentulous conditions . The mean scores of bone support , tooth mobility , and sulcular depths of abutment teeth were also similar . Significant but comparable improvements in oral hygiene and sulcular depth occurred in the two groups after treatment . The periodontal health scores at the 16-week interval serve as the baseline to measure subsequent changes in periodontal health . ( ABSTRACT TRUNCATED AT 400 WORDS CONTEXT Removable partial dentures used to restore the shortened lower dental arch may adversely affect the remaining natural teeth and are associated with a low prevalence of use . OBJECTIVE To report the findings for caries incidence 2 years after restoration of lower shortened arches with bilateral cantilever resin-bonded bridges ( RBBs ) and conventional partial dentures ( RPDs ) . DESIGN R and omised controlled trial . SETTING Secondary care PATIENTS 25 male and 35 female subjects of median age 67 years . were r and omly allocated to ' bridge ' and ' denture ' treatment groups of 30 patients each matched for age and sex . Caries incidence was recorded during dental examinations 3 months , 1 and 2 years after insertion of new lower prostheses . INTERVENTIONS Cantilever RBBs and conventional RPDs with cast metal frameworks . RESULTS There was a highly significant difference in the frequency of new caries lesions , 11 and 51 in the bridge and denture groups respectively ( P < 0.01 ) . 20 out of 27 bridge patients and 9 of 23 denture patients had no caries experience . Multivariate modeling identified treatment group as the only significant predictor of caries occurrence . CONCLUSIONS Two years after restoration of lower shortened arches for an elderly sample of patients , there was a significantly greater incidence of new and recurrent caries lesions in subjects restored with RPDs compared with cantilever RBBs PURPOSE The purpose of this study was to evaluate the effectiveness of the platform-switching technique to prevent crestal bone loss following the restoration of dental implants . MATERIAL S AND METHODS This r and omized prospect i ve multicenter trial analyzed 60 partially edentulous adults recruited at 12 professional dental centers . Subjects were r and omly selected to receive either platform-enlarged or control cylindric implants in three different surgical procedures : conventional nonsubmerged , submerged , and submerged with a reduced abutment . The primary outcome measure was the change in crestal bone level assessed radiographically 12 and 24 months following placement . Nonparametric analysis of variance for repeated measures ( the Friedman test ) was used to assess the overall significance over time of the differences among implants in changes in crestal bone levels . Comparisons among and between groups of implants were performed by the nonparametric Friedman and Wilcoxon tests , respectively . In all the analyses an alpha = .05 was considered significant . RESULTS A total of 360 implants were placed ( 60 for each group ) . Three control implants failed during the 2nd year following placement . All submerged and 92 % of nonsubmerged platform-enlarged implants exhibited no bone loss . Control implants with an abutment as large as the implant platform exhibited more bone loss than their platform-enlarged counterparts ( P < .001 ) or control implants with a reduced abutment ( P < .001 ) . Submerged implants with an enlarged platform showed better crestal bone preservation than submerged control implants with a reduced abutment ( P = .06 ) . CONCLUSIONS The findings of the current trial indicated that the use of implants with an enlarged platform can result in better preservation of crestal bone as compared with conventional cylindric implants when a reduced abutment is mounted STATEMENT OF THE PROBLEM An altered cast impression procedure to improve the support of distal extension removable partial dentures is widely taught , but not often used in dental practice . PURPOSE The purpose of this study was to determine the efficacy of an altered cast compared to a one-piece cast with regard to base support , abutment health , and patient comfort over time . MATERIAL AND METHODS Seventy-two patients receiving a m and ibular bilateral distal extension removable partial denture were assigned r and omly for treatment using either a one-piece or an altered cast . All impressions and associated laboratory procedures were made by one investigator . A second investigator evaluated extension , support , and adaptation of the denture bases by observation of border length and lifting of the indirect retainer from its seat . The space between the soft tissues and the base when the framework was related to the teeth was measured cross-sectionally at half the length of the denture base . Mobility , gingival index , and sulcus depths at 6 locations around each abutment tooth were recorded at insertion and again 1 year later . Chi-square tests were used to evaluate differences between the treatment groups ( alpha=.05 ) . RESULTS There was 0.15 mm less space between the ridge crest and base in the altered cast group ( P<.01 ) , and underextension of the base occurred only in the one-piece cast group ( P=.01 ) . At insertion , no tissue-ward movement was observed in 85 % of the prostheses when anterior-posterior rotation was attempted . Fifteen subjects ( 21 % ) were lost to recall at 1 year , but they were distributed equally between the 2 groups . Of the remaining 57 prostheses , 42 % exhibited decreased base support and 33 % had increased gingival inflammation ; the deepest probing depth decreased in 61 % , mobility decreased or remained the same in 80 % of the direct abutments , and 88 % of the subjects were satisfied . None of these findings were related to the impression procedure . CONCLUSION The altered cast impression procedure does not offer significant advantages over the one-piece cast , provided the st and ards used in this study are met . These include a completely extended impression , use of magnification to adjust and ensure complete seating of the framework , and coverage of the retromolar pad and buccal shelf by the base The two cements were of comparable performance This study examined the success of titanium ( Ti ) removable partial dentures ( RPDs ) compared with that of cobalt-chromium ( Co-Cr ) RPDs using a r and omized controlled clinical trial . Thirty-eight RPD patients were provided with either Co-Cr ( 20 patients ) or Ti ( 18 patients ) RPDs . The total numbers of dentures was 31 ( 13 maxillary , 18 m and ibular ) for Co-Cr and 23 ( 11 maxillary , 12 m and ibular ) for Ti . Patients were review ed for 24 months following denture issue . After the initial 12 months , 20 clinical problems were recorded and became the criteria for subsequent assessment . Incidence of failure was analysed using both Fisher 's exact test and the chi square test at a significance level of P<0.05 . Fracture of retainers in both metals occurred only in the first 12 months . Some failure types presented at significantly higher levels in the first 12 months but there were no significant differences between the two in all the criteria examined between the 12- and the 24-month review s. Although differences existed in failure types between Co-Cr and Ti RPDs during the early review stages , the overall success rate of Ti RPDs was comparable with that of Co-Cr RPDs after 24 months . The higher incidence of failures in Ti RPDs prior to the 12-month review suggests the importance of taking its lower rigidity into account when design ing RPDs PURPOSE The aim of this clinical study was to assess the marginal bone around two different types of implant-abutment junctions-a so-called platform-switched assembly and a conventional external-hexagon connection-after 24 months . MATERIAL S AND METHODS Forty-five patients were included in this prospect i ve study . All selected patients required the extraction of one or two hopeless teeth in maxillary and m and ibular region monoradicular and second premolar teeth , and were r and omly assigned to one of two groups . The first group received 34 implants with an external-hexagon junction with the abutment and the second group received 30 implants with platform-switched abutments . Implants were positioned immediately after tooth extraction and were loaded immediately . RESULTS After 24 months , a cumulative survival rate of 100 % was reported for all implants . The platform-switching group showed a mean bone loss of 0.78 + /- 0.49 mm and the external-hexagon group showed a mean bone loss of 0.73 + /- 0.52 mm ( no statistically significant difference between groups ) . CONCLUSION The results of this study indicate that implants placed immediately in fresh extraction sockets and loaded immediately represent a predictable procedure , with no differences in bone level changes between " platform-switched " and conventional external-hexagon implants after 24 months AIM To evaluate the soft tissue response to immediately placed implants using the platform switching concept . MATERIAL AND METHODS In 22 patients , 22 implants of 5.5 mm platform diameter were placed immediately into fresh extraction sockets in maxillae without compromised bone tissue . Eventual post- extraction bone defects were filled using bovine bone matrix mixed with collagen . Immediately after insertion , implants were r and omly divided : 11 implants were connected with a 3.8 mm diameter abutment ( test group ) and 11 with a 5.5 mm diameter abutment ( control group ) . A provisional crown was adapted and adjusted for non-functional immediate positioning . Two months later , definitive prosthetic rehabilitation was performed . Periodontal parameter , buccal peri-implant mucosal changes ( REC ) , mesial and distal papilla height ( PH ) and vertical height of jumping distance ( VHG ) were measured at the time of implant placement , of definitive prosthesis insertion and every 6 months thereafter . RESULTS The mean follow-up was 25 months . All implants were clinical ly osseointegrated . The test group showed a + 0.18 mm REC gain . PH gain was + 0.045 mm on average . The mean values were statistically significant ( P < or = 0.005 ) compared with the control group ( PH=-0.88 mm ; REC=-0.45 mm ) . No difference between the two groups in periodontal parameters was found . The mean value of bone filling was 7.51 mm in the test group ( 97.4 % of VHG ) and 8.57 mm in the control group ( 95.2 % of VHG ) . No statistically significant difference was found between the two groups . CONCLUSIONS This study suggests that , in a limited time period of 2 years , immediately placed implants with subsequent platform switching can provide peri-implant tissue stability Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor OBJECTIVES The objectives of this study were to investigate the impact of prosthetic rehabilitation of the shortened dental arch on the intake of nutrients , non-starch polysaccharide ( NSP ) fruits and vegetables ( dietary fibre ) , and to compare dietary intakes between patients receiving bilateral resin-bonded bridges with patients receiving conventional partial dentures . METHODS As part of an ongoing r and omised clinical trial to compare the effectiveness of bilateral resin bonded bridges with conventional partial dentures , the diets of 40 partially dentate patients were assessed prior to and at 3 and 12 months following treatment with bilateral resin-bonded bridge-work or a lower partial denture . RESULTS At baseline , three months post treatment and one year post treatment there were no significant differences in the intake of nutrients between groups . A significant increase in the percentage of energy from fat was observed in the patients fitted with a lower partial denture . Apart from this , prosthetic rehabilitation did not result in any other change in the intake of nutrients or in the amount of fruits and vegetables consumed . Levels of intake of NSP , fruits and vegetables were low in both groups of patients on all occasions measured . CONCLUSIONS Prosthetic rehabilitation of the severely shortened dental arch does not result in dietary improvements . Dietary advice that takes into account all the factors that influence food choice ( such as taste , cost and cooking skills ) needs to be considered in this at risk group STATEMENT OF PROBLEM Different material s ( autopolymerizing , dual curing , and light initiated ) are used for fabricating provisional restorations during prosthetic treatment . R and omized clinical trials that have evaluated these provisional material s have not been published . PURPOSE This clinical trial compared the h and ling , fitting , plaque adherence , gingivitis , color stability , and the subjective assessment of the provisional material s by the patient and the dentist for 2 autopolymerizing ( Protemp , Luxatemp ) , 1 dual-curing ( Provipont ) , and 1 light-initiated ( Triad-VLC ) material for the manufacturing of temporary crowns and fixed partial dentures . MATERIAL AND METHODS Thirty subjects in need of 2 similar fixed prosthetic restorations ( single crowns ¿ 20 , three-quarter crowns ¿ 2 , connected crowns ¿ 9 , or fixed partial dentures ¿ 30 ) were treated with 1 temporary restoration of Protemp II ( control ) and one r and omly selected from Luxatemp , Provipont , or Triad-VLC material s. The mean time of treatment was 37.5 days ( minimum 2 days , maximum 156 days ) . All restorations were manufactured intraorally with a vacuum-formed template . RESULTS Mechanical and retentive characteristics revealed a high level of clinical reliability . Plaque adherence of the teeth with temporary restorations was significantly increased ( P = .0039 ) compared with the untreated mesial reference teeth . CONCLUSION The advantageous mechanical properties of the light-curing and dual-curing material s review ed in dental literature were clinical ly offset by disadvantages in h and ling This clinical trial assessed the ability of Gluma Dentin Bond to inhibit dentinal sensitivity in teeth prepared to receive complete cast restorations . Twenty patients provided 76 teeth for the study . Following tooth preparation , dentinal surfaces were coated with either sterile water ( control ) or two 30-second applications of Gluma Dentin Bond ( test ) on either intact or removed smear layers . Patients were recalled after 14 days for a test of sensitivity of the prepared dentin to compressed air , osmotic stimulus ( saturated CaCl2 solution ) , and tactile stimulation via a scratch test under controlled loads . A significantly lower number of teeth responded to the test stimuli for both Gluma groups when compared to the controls ( P less than .01 ) . No difference was noted between teeth with smear layers intact or removed prior to treatment with Gluma OBJECTIVES A r and omized controlled clinical trial was undertaken , to study the influence of some patient- and operator-dependent variables on the survival of posterior resin-bonded bridges ( PRBBs ) and to assess the survival of replacement ' PRBBs . This report contains some of the results of the 5-year analysis . METHODS Survival was defined at three levels : ( 1 ) complete survival ( without any debonding ) , ( 2 ) functional survival ( i.e. survival after one loss of retention ) and ( 3 ) replacement survival ( survival of ' replacement ' PRBBs , inserted after rebonded bridges suffered a second dislodgement ) . Potential risk factors were analysed with Cox 's proportional hazards model and differences were tested for significance with the Breslow test . Observed effects are expressed as conditional-relative-risk ( CRR ) . Survival of ' replacement ' PRBBs was assessed with the Kaplan-Meier method . RESULTS Factors showing significant influences on complete survival were : ' location ' ( highest risk for m and ibular PRBBs : CRR = 2.2 ) , ' aetiology ' ( higher risk in treatment of aplasia : CRR = 2.9 ) , and ' time of existence ' ( open spaces existing less than 2 years before insertion of PRBB : CRR : 2.0 ) . The factor ' large open spaces in the m and ible ' was a risk for both complete and functional survival ( CCR values 3.1 and 3.5 , respectively ) . The survival of m and ibular and maxillary ' replacement ' PRBBs after 5 years was 19 + /- 7 % and 31 + /- 18 % , respectively . CONCLUSIONS Risk factors for PRBBs were : ' location ' , ' aetiology ' , ' time of existence ' , ' isolation method ' and ' large open spaces in the m and ible ' . M and ibular ' replacement ' PRBBs showed such an unacceptably low survival rate that fabrication is not recommended Recent observations suggest that less bone loss may result from placing a more medialized abutment on an implant ( platform switching ) . The objective of this study was to measure the radiographic crestal bone loss and biologic width around conventional and platform-switched implants . Implants were r and omly assigned into conventional or switched categories within the same prosthesis . Twenty-five implants were placed and observed in the m and ibles of 10 patients for 2 years . A regression analysis demonstrated a significant difference between groups ( P < or = .0001 ) . These findings suggest that less crestal bone loss occurs around a platform-switched dental implant versus a conventional implant Titanium ( Ti ) is a relatively new metal in prosthodontics . As a possible material for removable partial dentures ( RPDs ) , it was used in its pure form to make 10 RPDs which were compared with 10 identical cobalt-chromium ( Co-Cr ) alloy RPDs in a clinical trial . The dentures were used alternately for four weeks , the subjects were asked to answer a question naire and then the Co-Cr dentures were withdrawn . The Ti dentures were then followed up for 2 years and another st and ardized question naire administered . A survival rate of rests and retainers of 91 % was recorded and the dentures were found to be more comfortable ( 55 % ) and preferred ( 64 % ) than the Co-Cr dentures . Factors to increase the success rates are discussed PURPOSE The aim of the study was to compare results after 1 and 3 years when single crowns supported by CerAdapt ( test ) ceramic abutments or CeraOne ( control ) titanium abutments were loaded . MATERIAL S AND METHODS The material was divided into two groups : in group A , 69 ( 34 test , 35 control ) abutments/crowns from all involved clinics were followed for 1 year ; and in group B , 20 ( 10 test , 10 control ) abutments/crowns from one of the clinics were followed for 3 years . RESULTS No implant failed , giving a cumulative success rate of 100 % for the implants . Two CerAdapt abutments in group A fractured , giving a cumulative success rate of 93 % for the CerAdapt and 100 % for the CeraOne abutments after 1 year . No abutment failed in group B , giving a cumulative success rate of 100 % both for the CerAdapt and the CeraOne abutments between 1 and 3 years . The CerAdapt fractures might have been due to the fact that the abutments were impaired through too-extensive preparation and /or had been exposed to a too-high bending moment . Almost no marginal bone loss was recorded , indicating a stable bone situation both at CerAdapt and CeraOne abutments on single-tooth implants . Healthy conditions , with a relatively stable level of the periimplant mucosa in relation to the abutment/crown , were recorded for soft tissues both at CerAdapt and CeraOne abutments . Both clinicians and patients rated the esthetic result as excellent for practically all cases . CONCLUSION The results demonstrate the esthetic possibilities and the safety of single-tooth replacement when accepted treatment concepts are followed and documented components are used . The tested abutments worked well , although the fractured CerAdapt abutments indicate that ceramic abutments are more sensitive to h and ling procedures than the titanium abutments PURPOSE The purpose of this controlled prospect i ve clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels , peri-implant soft tissue parameters , and prosthetic complications . MATERIAL S AND METHODS Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova . They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width , similar bone height at the implant sites , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts . Each patient received 2 identical implants ( 1 in each edentulous site ) . One was r and omly selected to be restored with a cemented implant-supported single-tooth crown , and the other was restored with a screw-retained implant-supported single-tooth crown . Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention ( cemented versus screw-retained ) . RESULTS All patients completed the study . All 24 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters . DISCUSSION The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician 's preference . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population A Abbe flap \ăb # e flăp\ [ Robert Abbe , New York , N.Y. surgeon , 18511928 ] : eponym for a lip switch operation . A triangular , full thickness flap from the lower lip used to fill in a deficit in the upper lip . Specifically applied to the midportion of the upper or lower lip— called also lip switch operation Abbe , R. A new plastic operation for the relief of deformity due to double harelip . Med Rec 1898;53:477 . ab duct \ăb dŭkt#\ vt ( 1834 ) : to draw away from the median plane— comp ADDUCT ab er rant \ă-bĕr#ant\ adj ( ca . 1798)1 : a deviation from the normal or usual course , form , or location 2 : straying from the normal way ab frac tion \ăb frăk#shun\ n ( 1991 ) : the pathologic loss of hard tooth substance caused by biomechanical loading forces . Such loss is thought to be due to flexure and chemical fatigue degradation of enamel and /or dentin at some location distant from the actual point of loading — comp ABLATION , ABRASION , ATTRITION , and EROSION ab la tion \ă-bl a#shun\ n ( 15c ) 1 : separation or detachment ; extirpation ; eradication 2 : removal of a part , especially by cutting — see ABFRACTION , EROSION abrade \uh-br ad#\ vt ( 1677 ) : to rub away the external covering or layer of a part — comp ATTRITION , EROSION abra sion \ă-br a # shun\ n ( 1656 ) 1 : the wearing away of a substance or structure ( such as the skin or the teeth ) through some unusual or abnormal mechanical process 2 : an abnormal wearing away of the tooth substance by causes other than mastication — comp ATTRITION , EROSION abra sive \uh-br a # siv , -ziv\ n ( 1853 ) : a substance used for abrading , smoothing , or polishing abra sive \uh-br a # siv , -ziv\ adj ( 1875 ) 1 : tending to abrade 2 : causing irritation — abra sive ly adv , abra sive ness n ab ra si vity \uh-br a#siv-ı̆-t e , -ziv-ı̆-t e\ v ( 1998 ) : the property of one material to wear away another material by means of frictional contact absorbed dose \ab-sôrbd#,-zôrbd # d os\ : the amount of energy from ionizing radiation absorbed per unit mass of matter , expressed in Gray units ab sorp tance \ab-sôrp#tans , -zôrp#tans\ n ( ca . 1931 ) : the ratio of the radiant energy absorbed by a body to that incident upon it ab sorp tion \ab-sôrp#shun , -zôrp#-\ n ( 1741 ) 1 : the uptake of substances into or through tissues , e.g. , mucosa , skin , and intestine 2 : in radiology , the uptake of energy by matter with which the radiation interacts — see A. of RADIATION — comp ADSORPTION absorption of radiation \ab-sôrp#shun ŭv r a#d ea#shun\ : collisionlike interactions between the individual particulate or quantum components of a beam of radiation and the subatomic parts of matter that occur at r and om during irradiation . Each interaction may result in partial or complete transfer of energy abut ment \a-bŭt#ment\ n ( 1634 ) 1 : that part of a structure that directly receives thrust or pressure ; an anchorage2 : a tooth , a portion of a tooth , or that portion of a dental implant that serves to support and /or retain a prosthesis — usage see ANGULATED A. , HEALING A. , DENTAL IMPLANT A. , INTERMEDIATE A. , ONE PIECE A. , PREPARATION PIECE A. , ST AND ARD A. , TWO PIECE A. PURPOSE This prospect i ve clinical trial examined the effect on teeth and implants when rigidly or non-rigidly connected in a cross-arch model . MATERIAL S AND METHODS Thirty patients received 2 implants , 1 on each side of the m and ible , and were restored with 3-unit fixed partial dentures connected either rigidly or non-rigidly to an abutment tooth . Patients were followed for at least 5 years post-restoration . RESULTS Repeated- measures analysis revealed no significant difference in crestal bone loss at implants ( rigid versus non-rigid methods ) . An overall significant difference ( P < .001 ) was found comparing methods for teeth . Paired t tests revealed no significant differences in crestal bone levels for implants or teeth at the 5-year recall . Kaplan-Meier methods and the Cox proportional hazards model showed no differences between attachment methods with regard to success based on survival and bone loss criteria . During the 5-year recall period , 1 implant ( rigid side ) was removed . Four implants developed bone loss greater than 2 mm during the course of this trial . One tooth on the rigid side and 2 teeth on the non-rigid side had greater than 2 mm of crestal bone loss and were removed secondary to fractures . In all , 5 abutment teeth were removed , all of which had been treated with root canal therapy and fractured at the interface of the post within the tooth . There was no clear relationship of tooth fracture to attachment . Repeated- measures analysis of mobility values revealed no significant changes over the time course of this study , and paired t tests revealed no statistically significant differences between implants for mobility . Repeated- measures analysis and paired t tests for probing depth revealed no significant changes over the time course of this study . There were no significant differences in soft tissue indices for either attachment method . The percentage of patients who had measurable intrusion was 66 % for the non-rigid group , and 44 % for the rigid group ; 25 % of the non-rigid teeth had greater than 0.5 mm intrusion , compared with 12.5 % for the rigid group . For the 2 time periods evaluated , there was no significant increase in intrusion over time . The non-rigid-side implant required more nonscheduled visits to treat problems than the rigid implant and the teeth . DISCUSSION Most patients were treated successfully with rigid or non-rigid attachment of implants to teeth . CONCLUSION The high incidence of intrusion and non-scheduled patient visits suggest that alternative treatments without connecting implants to teeth may be indicated In 60 patients , 120 partial and full-coverage restorations were cemented on vital abutment teeth with either a glass ionomer or a zinc phosphate luting cement . A split-mouth design and a patient blind data acquisition protocol were used . During an average observation period of 17.3 months there were no differences between the two types of luting cements in regard to subjective and clinical parameters . A high incidence of postoperative hypersensitivity , which is often said to accompany the use of glass ionomer luting cements , was not observed . With the cementation method used in this study , the glass ionomer cement Ketac-Cem Maxicap was an acceptable alternative to conventional zinc phosphate cement . Capsule systems make the clinical h and ling of glass ionomer luting cements safe and easy and should be used routinely in dental practice Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges . Improved bonding procedures and preparation design s , however , may have a positive effect on the functional durability of these restorations . The present study reports the final analysis of a r and omized controlled clinical trial in which different design s of posterior resin-bonded bridges were evaluated for a period of at least 5 years . The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations . Survival in this study was defined at two levels : ( 1 ) ' complete ' survival ( survival without any debonding ) , and ( 2 ) ' functional ' survival ( survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding ) . With regard to ' complete ' survival , no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth ( etching/Clearfil F2 , s and blasting/Panavia EX , and silica-coating/Microfill Pontic C ) . The variable ' preparation form ' ( conventional preparation form vs. modified preparation form ) for complete survival was statistically in favor of the modified preparation form ( 62 % vs. 46 % ) , but did not influence the functional survival . With regard to ' functional ' survival , the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems ( 90 % survival vs. 72 % and 75 % , p < 0.01 ) . Factor location was found to be highly significant for both survival levels [ Cox 's PH model , p = 0.0002 ( Cox , 1972 ) ] : The five-year ' complete ' survival rates were 65 % for maxillary restorations and 40 % for m and ibular restorations , while the five-year ' functional ' survival rates were 89 % and 68 % , respectively . It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival . Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the m and ible . The bonding systems used in this study appear to have no influence on the chance of failure . In rebonded posterior resin-bonded bridges , the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested In a 10-year , multicenter , double-blind clinical trial , comparisons of the clinical behavior of crown and fixed partial denture restorations were made between a gold alloy and four less costly alternative alloys . The endpoints of interest were ( 1 ) the development of unacceptable ratings on any of 11 individual prosthodontic criteria and an overall rating , ( 2 ) the removal of the restoration , and ( 3 ) an event combining unacceptable overall rating and restoration removal . Each of 630 patients had two restorations completed , one from gold-palladium alloy and the other from one of four alternative alloys . The patients were enrolled during a period of 3 1/2 years , with some patients followed up as long as 10 years after restoration . Analysis of the endpoints showed that one of the alternative alloys was significantly poorer than the other material s for certain criteria A clinical trial using the experimental gingivitis model developed for periodontal clinical research was performed to evaluate the effect of a removable partial denture m and ibular major connector design on the surrounding gingival tissues . A comparison of the state of health of adjacent gingival tissues was made between the linguoplate ( control ) and cingulum bar ( test ) major connectors . Clinical parameters were recorded in a single-blind crossover experimental gingivitis trial . Subjects were brought to a level of optimal gingival health and then r and omly assigned to use one framework design while refraining from any oral hygiene . Measurements were made at 7-day intervals for 21 days . The subjects were returned to optimal oral health and repeated the experimental period with the alternate design . Results showed a greater increase in mean gingival inflammation with the control than with the test removable partial denture , suggesting that the cingulum bar has fewer detrimental effects on gingival tissues than the linguoplate major connector . Results of this study suggest that the experimental gingivitis model can be a useful and valid system for study ing the potential effects of a removable partial denture design on surrounding oral tissues This study assessed the efficacy of a 0.12 % chlorhexidine gluconate ( CHX ) rinse on the enhancement and maintenance of gingival health in patients receiving fixed prosthodontic treatment . Thirty patient participants in this examiner blind study were r and omly assigned into two groups , one control and another group using CHX 15 ml b.i.d . in addition to normal oral hygiene . The medication was used for 2 weeks prior to crown preparation , 3 weeks during provisional crown placement , and 2 weeks after definitive crown cementation . Plaque and gingivitis indices were measured initially and at the three aforementioned points during the 7-week period . The plaque index for the control group decreased by 0.26 units ; CHX decreased by 0.63 units at 7 weeks . The gingival index of the control group decreased by 0.37 units ; CHX decreased by 0.87 units . Adjunctive use of chlorhexidine with fixed prosthodontic procedures significantly reduced plaque levels and significantly improved gingival health compared with the control patients . Fixed prosthodontic procedures alone decreased plaque levels and increased gingival health This study assessed the changes of the subgingival/marginal microflora during fixed prosthodontic procedures and evaluated the effect of adjunctive rinsing with 0.12 % chlorhexidine on the subgingival/marginal microflora during fixed prosthodontic treatment . Thirty patients scheduled for fixed prosthodontics were r and omly assigned to either rinsing with 15 ml of tap water b.i.d . ( control ) or rinsing with 15 ml of 0.12 % chlorhexidine gluconate b.i.d . ( experimental ) . Subgingival and marginal plaque was analyzed at baseline , before crown preparation ( 2 weeks ) , before crown cementation ( 5 weeks ) , and 2 weeks after cementation ( 7 weeks ) . The fixed prosthodontic procedures alone altered the subgingival and marginal microbiota toward a more health-associated flora . Adjunctive rinsing twice daily with 0.12 % chlorhexidine had a significantly greater effect in reducing putative periodontal pathogens compared with the control regimen . This medication was a useful adjunct to regular oral hygiene during fixed prosthodontic procedures by permitting the establishment and maintenance of a microflora compatible with periodontal health OBJECTIVES The aim of this study was to test whether or not customized zirconia abutments exhibit the same survival rates in canine and posterior regions as titanium abutments , and to compare the esthetic result of the two abutment types . MATERIAL AND METHODS Twenty-two patients with 40 implants in posterior regions were included and the implant sites were r and omly assigned to 20 customized zirconia and 20 customized titanium abutments . All-ceramic ( AC ) and metal-ceramic ( MC ) crowns were fabricated . In all except two cases , the crowns were cemented on the abutments using resin or glass-ionomer cements . Two zirconia reconstructions were screw retained . At baseline , 6 and 12 months , the reconstructions were examined for technical and biological problems . Probing pocket depth ( PPD ) , plaque ( Pl ) and bleeding on probing ( BOP ) were assessed and compared with natural control teeth . Furthermore , the difference of color ( DeltaE ) of the peri-implant mucosa and the gingiva of control teeth was evaluated by means of a spectrophotometer ( Spectroshade ) . The data were analyzed with Student 's unpaired t-test , ANOVA and regression analyses . RESULTS Twenty patients with 19 zirconia and 12 titanium abutments were examined at a mean follow-up of 12.6+/-2.7 months . The survival rate for reconstructions and abutments was 100 % . No technical or biological problems were found at the test and control sites . Two chippings ( 16.7 % ) occurred at crowns supported by titanium abutments . No difference was found regarding PPD ( meanPPD(ZrO2 ) 3.4+/-0.7 mm , mPPD(Ti ) 3.3+/-0.6 mm ) , Pl ( mPl(ZrO2 ) 0.2+/-0.3 , mPl(Ti ) 0.1+/-1.8 ) and BOP ( mBOP(ZrO2 ) 60+/-30 % , mBOP(Ti ) 30+/-40 % ) between the two groups . Both crowns on zirconia and titanium abutments induced a similar amount of discoloration of the soft tissue compared with the gingiva at natural teeth ( DeltaE(ZrO2 ) 8.1+/-3.9 , DeltaE(Ti ) 7.8+/-4.3 ) . CONCLUSIONS At 1 year , zirconia abutments exhibited the same survival and a similar esthetic outcome as titanium abutments |
421 | 29,930,701 | There is also an urgent need to investigate how best improvements in knowledge and skills can be translated into behavioural change | Suicide is a leading cause of death in adolescence .
School provides an effective avenue both for reaching adolescents and for gatekeeper training .
This enables gatekeepers to recognize and respond to at-risk students and is a meaningful focus for the provision of suicide prevention .
This study provides the first systematic review on the effectiveness of school-based gatekeeper training in enhancing gatekeeper-related outcomes . | This study employed a self-report question naire in a Solomon four-groups design to assess the efficacy of suicide intervention classes in achieving their instructional objectives . Because adolescents are often the first to know of a peer 's suicidal thoughts or plans , the goal of the classes was to increase the likelihood that students who come into contact with potentially suicidal peers can more readily identify them and will be consistently inclined to take responsible action on their behalf . Students who participated in the classes as compared to controls showed significant gains in relevant knowledge about suicidal peers and significantly more positive attitudes toward help seeking and intervening with troubled peers . Results of this study will be used to strengthen components of the lessons aim ed at enhancing the likelihood of performance of responsible interventions Gatekeeper-training programs , design ed to increase identification and referral of suicidal individuals , are widespread but largely untested . A group-based r and omized trial with 32 schools examined impact of Question , Persuade , Refer ( QPR ) training on a stratified r and om sample of 249 staff with 1-year average follow-up . To test QPR impact , the authors introduced and contrasted 2 models of gatekeeper-training effects in a population : gatekeeper surveillance and gatekeeper communication . Intent-to-treat analyses showed that training increased self-reported knowledge ( effect size [ ES ] = 0.41 ) , appraisal s of efficacy ( ES = 1.22 ) , and service access ( ES = 1.07 ) . Training effects varied dramatically . Appraisal s increased most for staff with lowest baseline appraisal s , and suicide identification behaviors increased most for staff already communicating with students about suicide and distress . Consistent with the communication model , increased knowledge and appraisal s were not sufficient to increase suicide identification behaviors . Also consistent with the communication model were results from 2,059 8th and 10th grade rs surveyed showing that fewer students with prior suicide attempts endorsed talking to adults about distress . Skill training for staff serving as " natural gatekeepers " plus interventions that modify students ' help-seeking behaviors are recommended to supplement universal gatekeeper training Suicide is a major public health problem . Nationally , suicide is the third leading cause of death for adolescents . The purpose of this quality improvement project was to initiate and evaluate a gatekeeper suicide-prevention program within a local school system targeting faculty and staff without a medical or psychology background who interact regularly with middle- and high-school students . Following the implementation of this program , evaluation of increased knowledge related to adolescent suicide prevention was completed . All participants completed a pretest and posttest , and results indicate that the staff members ' knowledge about identification of risk factors , behavioral responses to suicidal students , and knowledge of community re sources were increased . This project highlights the need for planned and sustainable education and training for faculty and school staff who regularly interact with adolescents . Additionally , the importance of continued monitoring , training , and advocating for suicide prevention programming is noted OBJECTIVE To examine symptomatology and mental health service use following students ' contact with a large urban school district 's suicide prevention program . METHOD In 2001 school district staff conducted telephone interviews with 95 r and omly selected parents approximately 5 months following their child 's contact with the district 's suicide prevention program , a School Gatekeeper Training model . Parents provided information regarding service use , their child 's depressive symptoms ( using the Diagnostic Interview Schedule for Children Predictive Scale , Depression module ) , and their perceptions of their child 's need for services . Information about the crisis intervention was abstract ed from a st and ardized assessment form . RESULTS More than two thirds of students received school or community mental health services following contact with the suicide prevention program . Depressive symptoms , but not past year suicide attempt , predicted community mental health service use . Latino students had lower rates of community mental health service use than non-Latinos . School-based service use did not differ by student characteristics including race/ethnicity . CONCLUSIONS Most students identified by a school-based suicide prevention program received follow-up care , although Latinos were less likely to access services outside the school . School-based mental health services may be an important way in which underserved population s at risk of suicide can receive care A national r and om sample of 228 high school health teachers completed a 45-item survey to examine their perceived self-efficacy regarding adolescent suicide . Most respondents were female , White , and held master 's degrees . Most believed it was their role to recognize students at risk for suicide , believed that if they did recognize students at risk it would reduce the chances that the student would commit suicide , and believed that one of the most important things they could do would be to prevent a suicidal student from committing suicide . However , only 9 % believed they could recognize a student at risk for suicide . High efficacy expectations scores were associated with working at a school that offered an inservice program on adolescent suicide , included teaching about suicide prevention in the curriculum , and had a crisis intervention team . This study suggests that teacher health education programs should spend more time on developing the skills necessary to identify students at risk . In addition , a comprehensive school suicide prevention program is strongly encouraged for all high schools Background The traditional wait-listed design , where half are r and omly assigned to receive the intervention early and half are r and omly assigned to receive it later , is often acceptable to communities who would not be comfortable with a notreatment group . As such this traditional wait-listed design provides an excellent opportunity to evaluate short-term impact of an intervention . We introduce a new class of wait-listed design s for conducting r and omized experiments where all subjects receive the intervention , and the timing of the intervention is r and omly assigned . We use the term “ dynamic wait-listed design s ” to describe this new class . Purpose This paper examines a new class of statistical design s where r and om assignment to intervention condition occurs at multiple times in a trial . As an extension of a traditional wait-listed design , this dynamic design allows all subjects to receive the intervention at a r and om time . Motivated by our search for increased statistical power in an ongoing school-based trial that is testing a program of gatekeeper training to identify suicidal youth and refer them to treatment , this new design class is especially useful when the primary outcome is a count or rate of occurrence , such as suicidal behavior , whose rate can fluctuate over time due to uncontrolled factors . Methods Statistical power is computed for various dynamic wait-listed design s under conditions where the underlying rate of occurrence is allowed to vary non systematic ally . We also present as an example a large ongoing trial to evaluate a gatekeeper training suicide prevention program in 32 schools which we initially began as a classic r and omized wait-listed design . The primary outcome of interest in this study is the count of the number of children who are identified by the school system as having suicidal thoughts or behaviors who are then vali date d as being suicidal by mental health professionals in the community . Results A general result shows that dynamic wait-listed design s always have higher statistical power over a traditional wait-listed design . This power increase can be substantial . Efficiency gains of 33 % are easy to obtain for situations where the intervention has a small effect and the variation in rate across time is quite high . When the rate variation for an outcome is very low or the intervention effect is large , efficiency gains approach 100 % . A small increase in the number of times where r and om assignment occurs from 2 – for the st and ard wait-listed design , to say 4 – can provide a large reduction in variance . Efficiency gains can also be high when converting st and ard wait-listed design to a dynamic one half-way into the study . Limitations As with all wait-listed design s , dynamic wait-listed design s can only be used to evaluate short-term impact . Since all subjects eventually receive the intervention , no comparison can be made after the end of the r and om assignment period . The statistical power benefits are primarily limited to outcomes that can be treated as count or time to event data . Conclusions A dynamic design r and omly assigns units – either individuals or groups – to start the intervention at varying times during the course of the study . This design is useful in testing interventions that screen for new or existing cases , as well as testing the scalability of interventions as they are disseminated or exp and ed system wide . They can improve on the traditional wait-listed design both in terms of statistical power and robustness in the presence of exogenous factors . This paper demonstrates that such design s yield smaller st and ard errors and can achieve higher statistical power than that of a st and ard wait-listed design . Just as important , dynamic design s can also help reduce the logistical challenges of implementing an intervention on a wide scale . When the intervention requires that significant training re sources be allocated throughout the study , the dynamic waitlisted design is likely to increase the rate of training and lead to a higher level of program implementation Objectives : To evaluate a suicide prevention training workshop for staff working in the field of traumatic brain injury ( TBI ) and to develop new measures for evaluation of similar training in the future . Design : A prospect i ve controlled pre- and posttest evaluation with a 6-month follow-up . Subjects : Multidisciplinary TBI rehabilitation and disability staff from the state of Victoria attending the workshop ( n = 50 ) and an equivalent control group ( n = 28 ) recruited from New South Wales . Setting : A statewide training workshop was held at a major rehabilitation center in Melbourne . Outcome measures : Three design ed measures including an objective knowledge test , a self- assessment inventory of knowledge/skills and an attitudinal inventory . Results : Participants recorded statistically significant increases in their scores comparing the pre- to postworkshop evaluations . Many of these gains were maintained at the 6-month follow-up evaluation . In contrast , the control group had scores equivalent to those of workshop participants on the pretest evaluations but recorded no similar increase at follow-up . Factor analysis found that the knowledge and skills self- assessment inventory had 2 factors , each having good internal reliability . Conclusion : The current workshop has proved effective in increasing staff knowledge and skills in the assessment and management of people with TBI exhibiting suicidal behaviors . Finally , the initial development of a knowledge and skills self- assessment measure shows promise , providing a re source for the ongoing evaluation of suicide prevention training in the TBI field In this pilot study we report on proximate outcomes of a 1-hour community gatekeeper training in-service for 76 non clinical employees in a university hospital workplace setting . Pre-post analyses result ed in positive changes in participants ' knowledge about suicide and attitudes ( self-efficacy ) about intervening with suicidal individuals . A subset of participants engaged in role play practice of gatekeeper skills following training and rated the experience positively . Fifty-five observations were rated using an observational measure developed for this study and approximately half of these demonstrated satisfactory skills post training . Participants in this workplace gatekeeper training reported sharing new knowledge and skills with family , friends , and coworkers The purpose of this article was to describe patterns of poor mental health/depression ( PMHD ) in a national sample of college students and the relationships among PMHD , alcohol consumption , harm , and abuse . Responses to mailed question naires completed by a r and om sample of 27,409 students at 119 colleges were analyzed using logistic regression . Nationally , 4.8 % of students reported PMHD . The average college prevalence was 5.01 % ( range , 0.68 % to 13.23 % ) . Students with PMHD were more likely than their peers to be female , nonwhite , and from low socioeconomic status families ; less likely to report never drinking ; as likely to report frequent , heavy , and heavy episodic drinking ; and more likely to report drinking to get drunk . Students with PMHD — especially females — were more likely to report drinking-related harms and alcohol abuse . College is a critical context for study ing youth mental health . The interrelationship of mental health problems and their clustering by group and college are important considerations for prevention and treatment BACKGROUND Suicide is a significant public health problem worldwide that requires evidence -based prevention efforts . One approach to prevention is gatekeeper training . Gatekeeper training programs for community members have demonstrated positive changes in knowledge and attitudes about suicide . Changes in gatekeeper skills have not been well established . AIMS To assess and to predict the impact of a brief , gatekeeper training on community members ' observed skills . METHODS Participants in a community gatekeeper training were employees at US universities . 50 participants were r and omly selected for skills assessment and videotaped interacting with a st and ardized actor prior to and following training . Tapes were reliably rated for general and suicide-specific skills . RESULTS Gatekeeper skills increased from pre- to posttest : 10 % of participants met criteria for acceptable gatekeeper skills before training , while 54 % met criteria after training . Pretraining variables did not predict increased skills . LIMITATIONS Results do not provide conclusions about the relationship between observed gatekeeper skills and actual use of those skills in the future . CONCLUSIONS Gatekeeper training enhances suicide-specific skills for the majority of participants . Other strategies , such as behavioral rehearsal , may be necessary to enhance skills in the remaining participants BACKGROUND Gatekeeper suicide prevention programs train staff to increase the identification and referral of suicidal individuals to the appropriate re sources . AIMS We evaluated Act on FACTS : Making Educators Partners in Youth Suicide Prevention ( MEP ) , which is an online training program design ed to enhance the knowledge of suicide risk factors and warning signs as well as improve participants ' attitudes and self-efficacy/confidence . METHOD School personnel ( N = 700 ) completed a survey administered before and immediately after the training to assess gains in training outcomes and to evaluate participants ' satisfaction with the training . RESULTS Results indicated that MEP participants demonstrated significant increases in suicide knowledge , attitudes , and self-efficacy . Moreover , exploratory analyses revealed moderating effects of professional role on pre-/posttest changes in self-efficacy , but not suicide knowledge or attitudes . Specifically , guidance counselors demonstrated significantly smaller increases in self-efficacy/confidence compared with teachers and classroom aids , whereas teachers demonstrated significantly larger increases in self-efficacy/confidence compared with administrators . The majority of school personnel who completed the MEP program were satisfied with the training content and experience . CONCLUSION Although the current findings are promising , more rigorous evaluations employing r and omized controlled research design s are warranted to adequately determine the effectiveness of the MEP program |
422 | 29,972,239 | US-CNB is a superior diagnostic technique to US-FNA for axillary staging in breast cancer | BACKGROUND Axillary lymph node status remains a significant prognostic indicator in breast cancer .
Here , the diagnostic accuracy of ultrasound-guided fine-needle aspiration ( US-FNA ) and ultrasound-guided core needle biopsy ( US-CNB ) in axillary staging was compared . | BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present st and ard . Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects . We aim ed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects . METHODS Patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy were enrolled in the r and omised , multicentre , open-label , phase 3 non-inferiority EORTC 10981 - 22023 AMAROS trial . Patients were r and omly assigned ( 1:1 ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution . The primary endpoint was non-inferiority of 5-year axillary recurrence , considered to be not more than 4 % for the axillary radiotherapy group compared with an expected 2 % in the axillary lymph node dissection group . Analyses were by intention to treat and per protocol . The AMAROS trial is registered with Clinical Trials.gov , number NCT00014612 . FINDINGS Between Feb 19 , 2001 , and April 29 , 2010 , 4823 patients were enrolled at 34 centres from nine European countries , of whom 4806 were eligible for r and omisation . 2402 patients were r and omly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy . Of the 1425 patients with a positive sentinel node , 744 had been r and omly assigned to axillary lymph node dissection and 681 to axillary radiotherapy ; these patients constituted the intention-to-treat population . Median follow-up was 6·1 years ( IQR 4·1 - 8·0 ) for the patients with positive sentinel lymph nodes . In the axillary lymph node dissection group , 220 ( 33 % ) of 672 patients who underwent axillary lymph node dissection had additional positive nodes . Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group . 5-year axillary recurrence was 0·43 % ( 95 % CI 0·00 - 0·92 ) after axillary lymph node dissection versus 1·19 % ( 0·31 - 2·08 ) after axillary radiotherapy . The planned non-inferiority test was underpowered because of the low number of events . The one-sided 95 % CI for the underpowered non-inferiority test on the hazard ratio was 0·00 - 5·27 , with a non-inferiority margin of 2 . Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year , 3 years , and 5 years . INTERPRETATION Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy . Axillary radiotherapy results in significantly less morbidity . FUNDING EORTC Charitable Trust PURPOSE To compare the diagnostic accuracy of ultrasonographically (US)-guided fine-needle aspiration biopsy ( FNAB ) and core-needle biopsy ( CNB ) of the axillary lymph nodes ( LNs ) of patients with newly diagnosed invasive breast cancer . MATERIAL S AND METHODS This prospect i ve single-center study had institutional review board approval , and written informed consent was obtained . Between April 2011 and March 2012 , 178 consecutive patients ( 182 axillae ) were evaluated by using axillary US . Sixty-six axillae fulfilled the inclusion criteria ( cortical thickness greater than 2 mm or abnormal morphologic characteristics ) , and patients with these axillae underwent US-guided axillary LN biopsy . Both FNAB and CNB were obtained from the same suspicious LN . Patients with biopsy-proved metastasis underwent axillary clearance , and those with a negative biopsy underwent sentinel LN biopsy with completion axillary clearance if needed . Diagnostic performance was calculated separately for US , FNAB , and CNB . Statistical differences in sensitivities were evaluated by using the McNemar test . RESULTS From the total study population , 45.6 % ( 83 of 182 axillae ) had metastases . A total of 66 axillae underwent both FNAB and CNB . The sensitivity for US was 61.4 % ( 51 of 83 axillae ) , and specificity was 84.8 % ( 84 of 88 axillae ) . The sensitivities for FNAB and CNB were 72.5 % ( 37 of 51 axillae ) and 88.2 % ( 45 of 51 axillae ) , respectively ( P = .008 ) . Specificity for both was 100 % ( 15 of 15 axillae ) . The negative predictive value for FNAB was 81.7 % , and that for CNB was 91.2 % . The positive predictive value was 100 % for both methods . CONCLUSION When accurate preoperative staging of the axilla is needed in patients with newly diagnosed invasive breast cancer , CNB is more sensitive than FNAB CRA506 Background : Sentinel node biopsy ( SNB ) eliminates the need for axillary dissection ( ALND ) in patients whose sentinel node ( SN ) is tumor-free . However , completion ALND remains the gold st and ard for patients with a tumor-involved sentinel node . ALND achieves regional control , but its effect on survival remains controversial . The main objective of ACOSOG Z0011 was to compare outcomes of patients with hematoxylin and eosin ( H&E ) detected metastasis in SN managed with or without ALND and no axillary irradiation . METHODS Clinical ly node-negative patients who underwent SN biopsy and had 1 or 2 SN with metastases detected by H&E were r and omized to ALND or no further axillary specific treatment . All patients were treated with lumpectomy and opposing tangential field irradiation . Adjuvant systemic therapy was at the discretion of their physicians . Overall survival ( OS ) , disease-free survival ( DFS ) , and locoregional control were evaluated . RESULTS 446 patients were r and omized to SNB alone and 445 to SNB plus ALND . Patients treated with SNB alone were similar to those treated with SNB + ALND with respect to age , tumor size , Bloom-Richardson score , estrogen receptor status , adjuvant systemic therapy , tumor type , and T stage . Patients r and omized to SNB alone had a median of two lymph nodes removed whereas patients r and omized to ALND had a median of 17 lymph nodes removed . 17.6 % of ALND patients had 3 or more involved nodes compared to 5.0 % of SNB patients ( p < 0.001 ) . Median follow-up is 6.2 years . 5-year in breast recurrence after ALND was 3.7 % compared to 2.1 % for SNB ( p = 0.16 ) while 5-year nodal recurrence was 0.6 % compared to 1.3 % ( p = 0.44 ) respectively . The five-year OS for patients undergoing SNB + ALND is 91.9 % compared to 92.5 % for SNB alone ( p = 0.24 ) , and DFS is 82.2 % compared to 83.8 % respectively ( p = 0.13 ) . CONCLUSIONS Despite the widely held belief that ALND improves survival , no significant difference was recognized by this study of SN node-positive women . Although the study closed early because of low accrual/event rate , it is the largest phase III study of ALND for node-positive women , and it demonstrates no trend toward clinical benefit of ALND for patients with limited nodal disease . [ Table : see text ] Ultrasound ( US ) is more sensitive than physical examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma . Due to occasional overlap of sonographic features of benign and indeterminate lymph nodes , fine‐needle aspiration ( FNA ) of sonographically indeterminate/suspicious lymph nodes can provide a more definitive diagnosis than US alone . This study was undertaken to determine the diagnostic accuracy of US‐guided FNA of indeterminate/suspicious/metastatic‐appearing axillary lymph nodes during the initial staging of breast carcinoma 96 Background : The sensitivity and specificity of FNAB and CNB performed in suspicious axillary LNs have ranged from 56 % to 86 % and from 91 % to 100 % , because FNAB and CNB are operator- and institution-dependent procedures . In addition , previous studies concerning the diagnostic accuracy of these procedures have reported results from only FNAB or CNB . So , the purpose of this study was to determine the diagnostic accuracy of axillary US and compare that of US-guided FNAB with CNB for axillary staging in the same breast cancer population . METHODS Of 220 breast cancer patients who underwent preoperative or prechemotherapy axillary US for axillary staging , 52 patients who underwent US-guided FNAB and CNB of cortical thickening and /or compressed hilum of lymph nodes on US were prospect ively enrolled . US and FNAB/CNB findings were compared with final pathology from sentinel lymph node biopsy or axillary lymph node dissection . RESULTS Forty-eight patients met the final study criteria ; we excluded 4 who had received primary systemic chemotherapy and showed negative FNAB/CNB results with negative final post-operative pathology . Positive predictive value ( PPV ) of axillary US was 54 % . The sensitivity and specificity of FNAB were 73 % and 100 % , and those of CNB were 77 % and 100 % . Results did not significantly differ between US-guided CNB and FNAB . The complication rates of FNAB and CNB were 4 % , and FNAB and CNB cost $ 180 and $ 350 , respectively . CONCLUSIONS Both US-guided CNB and FNAB were useful for axillary staging in breast cancer patients with high sensitivity . However , FNAB is recommended based on the advantages of low cost and minimal invasiveness 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 OBJECTIVE Diagnosis of axillary nodal involvement is significant in the management of breast cancer as well as in predicting prognosis . In this prospect i ve study , we evaluated the efficiency of US-guided fine needle aspiration biopsy ( FNAB ) in preoperative axillary staging of early breast cancer . MATERIAL AND METHODS Between January 2011 and July 2013 , 46 women were prospect ively enrolled in the study . Ultrasound guided-FNABs for axillary assessment were performed preoperatively . Cytology results were compared with histopathology reports to determine its sensitivity , specificity , negative and positive predictive value and accuracy . RESULTS Nineteen cases that had malignant cytology on FNAB also had axillary involvement in axillary lymph node dissection ( ALND ) without any false-positive results . The sensitivity and specificity of US-guided FNAB were 63.3 % and 100 % , respectively . US-guided FNAB was accurate in predicting the status of the axilla in 76.1 % of patients . CONCLUSION Although this technique is favorable due to its minimally invasive nature , it is not as effective as sentinel lymph node biopsy ( SLNB ) in terms of detecting axillary metastasis preoperatively . The low sensitivity and low accuracy rates decrease the usefulness of the technique . Therefore , it seems that US-guided FNAB alone could not replace SLNB . Nevertheless , combining some other molecular studies may be useful in increasing the technique 's sensitivity . These issues should be determined by comprehensive clinical trials INTRODUCTION Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy ( SLNB ) . Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology ( AUS/FNAC ) may represent a higher axillary disease burden m and ating an axillary clearance and thus an upfront SLNB may be avoided . The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance ( ALND ) based on ACOSOG Z011 criteria . METHODS A retrospective review of a prospect ively maintained data base identified patients with positive pre-operative AUS/FNAC between 2007 and 2012 . Core biopsies were excluded . Demographic and tumour characteristics were analysed . Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified . RESULTS 432 patients were identified with positive AUS/FNAC . 85 patients were excluded leaving 347 for analysis . Median age was 56 years ( 22 - 87 ) , median tumour size was 25 mm ( 1.5 mm-150 mm ) and median tumour pathology was grade 3 ( 50 % ) and invasive ductal carcinoma ( 82 % ) . Median number of nodes removed at ALND was 23 ( 1 - 55 ) with a median number of positive nodes being 4 ( 1 - 47 ) . 134 ( 39 % ) patients had ≤2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study . When other ACOSOG Z011 exclusion factors were applied only 27 ( 7.8 % ) patients may have avoided ALND . CONCLUSIONS Nodal positivity on AUS/FNAC is associated with higher axillary disease burden . Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary Purpose The purpose of this study was to investigate the accuracy of preoperative diagnostic tools for axillary lymph nodes ( LNs ) staging of breast cancer . Material s and Methods A total of 2464 consecutive patients with operable breast cancer were prospect ively identified at our institution between April 2012 and March 2017 . Patients with suspicious axillary LN of breast cancer were assessed using preoperative ultrasound(US ) or computed tomography ( CT ) , underwent fine-needle aspiration cytology ( FNA ) or core needle biopsy ( CNB ) . The inclusion criteria for both FNA and CNB were a cortical thickness > 3 mm or abnormal morphological characteristics . Patients with biopsy-proven metastasis underwent axillary lymph node dissection ( ALND ) , and those with a negative FNA or CNB underwent sentinel lymph node biopsy ( SNB ) . If the SNB was positive , ALND was performed . Diagnostic accuracy for SNB was calculated for both FNA and CNB . In addition , the patients in this study were divided into two groups as follows : the cN0-FNA group ( suspicious LN but negative FNA ) and cN0-CNB group ( suspicious LN but negative CNB ) . Results A number of patients with negative US/CT findings of LNs were 1406 , with 744 undergoing FNA and 272 undergoing CNB for suspicious LNs . Sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and accuracy were 65 , 99 , 99 , 80 , and 85 % in FNA , and 87 , 100 , 100 , 93 and 95 % in CNB , respectively . SNB was performed in 172 ( cN0-CNB group ) of 272 CNB and 487 ( cN0-FNA group ) of 744 FNA patients . One hundred and seventy-two patients from the cN0-CNB group ( Tis 6 , T1 97 , T2 66 , T3 3 patients ) treated with SNB were compared to 487 from the cN0-FNA group ( Tis 21 , T1 225 , T2 233 , T3 8 patients ) in terms of number of LN metastasis . A number of patients with more than 3 positive SNB and positive LNs were 9 ( 5 % ) and 0 ( 0 % ) in cN0-CNB group , and 78 ( 16 % ) and 24 ( 5 % ) in cN0-FNA group , respectively . A number of patients who had complications such as haematoma and pain at the time of 7 to 14 days after CNB and FNA were 1 ( 0.5 % ) and 1 ( 0.5 % ) in cN0-CNB group , and were 0 % and 0.2 % in cN0-FNA group ( p = 0.44 ) , respectively . Conclusions The preoperative diagnosis of axillary LNs was influenced by the diagnostic tool used . CNB is a reliable method for the preoperative diagnosis of LN metastasis IMPORTANCE Sentinel lymph node ( SLN ) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection ( ALND ) for patients with clinical ly node-negative ( cN0 ) breast cancer . The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies . OBJECTIVE To determine the false-negative rate ( FNR ) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer . DESIGN , SETTING , AND PATIENTS The American College of Surgeons Oncology Group ( ACOSOG ) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4 , N1 through N2 , M0 breast cancer and received neoadjuvant chemotherapy . Following chemotherapy , patients underwent both SLN surgery and ALND . Sentinel lymph node surgery using both blue dye ( isosulfan blue or methylene blue ) and a radiolabeled colloid mapping agent was encouraged . MAIN OUTCOMES AND MEASURES The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease . We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10 % , the rate expected for women undergoing SLN surgery who present with cN0 disease . RESULTS Seven hundred fifty-six women were enrolled in the study . Of 663 evaluable patients with cN1 disease , 649 underwent chemotherapy followed by both SLN surgery and ALND . An SLN could not be identified in 46 patients ( 7.1 % ) . Only 1 SLN was excised in 78 patients ( 12.0 % ) . Of the remaining 525 patients with 2 or more SLNs removed , no cancer was identified in the axillary lymph nodes of 215 patients , yielding a pathological complete nodal response of 41.0 % ( 95 % CI , 36.7%-45.3 % ) . In 39 patients , cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND , result ing in an FNR of 12.6 % ( 90 % Bayesian credible interval , 9.85%-16.05 % ) . CONCLUSIONS AND RELEVANCE Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined , the FNR was not found to be 10 % or less . Given this FNR threshold , changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00881361 OBJECTIVE The purpose of this study is to determine lymph node features on axillary ultrasound ( US ) images obtained after neoadjuvant chemotherapy that are associated with residual nodal disease in patients with initial biopsy-proven node-positive breast cancer . SUBJECTS AND METHODS All patients had axillary US performed after neoadjuvant chemotherapy . Axillary US images were central ly review ed for lymph node size , cortical thickness , and cortical morphologic findings ( type I indicated no visible cortex ; type II , a hypoechoic cortex ≤ 3 mm ; type III , a hypoechoic cortex > 3 mm ; type IV , a generalized lobulated hypoechoic cortex ; type V , focal hypoechoic cortical lobulation ; and type VI , a totally hypoechoic node with no hilum ) . Lymph node characteristics were compared with final surgical pathologic findings . RESULTS Axillary US images obtained after neoadjuvant chemotherapy and surgical pathologic findings were available for 611 patients . Residual nodal disease was present in 373 patients ( 61.0 % ) , and 238 ( 39.0 % ) had a complete nodal pathologic response . Increased cortical thickness ( mean , 3.5 mm for node-positive disease vs 2.5 mm for node-negative disease ) was associated with residual nodal disease . Lymph node short-axis and long-axis diameters were significantly associated with pathologic findings . Patients with nodal morphologic type I or II had the lowest rate of residual nodal disease ( 51 of 91 patients [ 56.0 % ] and 138 of 246 patients ( 56.1 % ) , respectively ) , whereas those with nodal morphologic type VI had the highest rate ( 44 of 55 patients [ 80.0 % ] ) ( p = 0.004 ) . The presence of fatty hilum was significantly associated with node-negative disease ( p = 0.0013 ) . CONCLUSION Axillary US performed after neoadjuvant chemotherapy is useful for nodal response assessment , with longer short-axis diameter , longer long-axis diameter , increased cortical thickness , and absence of fatty hilum significantly associated with residual nodal disease after neoadjuvant chemotherapy |
423 | 30,244,337 | Conclusions UG-PCNL is as effective as FG-PCNL and has the advantage of lower complication rates .
In addition , UG-PCNL could be performed with patients in the supine position without compromising its efficacy | Purpose To evaluate the efficacy and safety of ultrasound-guided ( UG ) versus fluoroscopy-guided ( FG ) percutaneous nephrolithotomy ( PCNL ) . | Objectives : To compare the success and complication rates of sonography-guided supine percutaneous nephrolithotomy ( PCNL ) versus prone st and ard technique ( fluoroscopic guidance ) in a r and omized controlled trial . Subjects and Methods : Between April 2009 and August 2011 , 92 c and i date s for PCNL were r and omly divided into two groups : 46 B-mode sonography-guided supine PCNL ( group A ) and 46 st and ard fluoroscopic-guided prone PCNL ( group B ) . Demographic , clinical and perioperative patient characteristics were analyzed , and complications and success rates were compared between the two approaches . Results : Preoperative parameters were comparable in the two groups . The primary success rate was 79.0 and 65.2 % in groups A and B , respectively , after one session of PCNL ( p = 0.485 ) . Sonography-guided access failed in 3 cases ( failure rate 6.5 % in group A vs. 0 % in group B ) . Mean hospital stay ( 2.48 days for group A vs. 2.95 days for group B ; p = 0.039 ) and mean nephrostomy tube stay time ( 1.79 days for group A vs. 2.56 days for group B ; p = 0.007 ) were significantly prolonged in the st and ard technique . Postoperative fever was more prevalent in the st and ard PCNL group ( p = 0.024 ) , but no significant difference was observed in other complications between the two groups . Conclusion : In this study , sonography-guided supine PCNL was presented as a safe and effective technique , similar to st and ard PCNL , with comparable success and complication rates . In addition , using this technique eliminates the possible harmful impacts of radiation on the surgical team and decreases postoperative fever BACKGROUND AND PURPOSE Gaining access to the pyelocaliceal system in percutaneous nephrolithotomy ( PCNL ) is routinely performed using fluoroscopic guidance with the patient in a prone position . We compared ultrasonography-guided access for PCNL with the patient in the flank position with conventional fluoroscopy-guided access . PATIENTS AND METHODS A total of 60 patients were r and omly separated into two 30-patient groups -- namely , ultrasonography-guided access with the patient in the flank position as group 1 , and fluoroscopy-guided access with the patient in the prone position as group 2 . In group 1 , the entire procedure was performed under ultrasonography guidance . RESULTS Successful access was achieved 100 % in both groups . The success rate was 86.7 % in group 1 and 90 % in group 2 ( P = 0.45 ) . The residual stone rate ( stone > or=4 mm ) was 13.3 % in group 1 and 10 % in group 2 . The access duration was 14.5 + /- 2.6 minutes and 9.4 + /- 2.3 minutes in groups 1 and 2 , respectively ( P < 0.05 ) . No significant differences for complications without any adjacent injuries were detected in both groups . Furthermore , the average hospital stay was 2.7 + /- 0.3 and 2.9 + /- 0.3 days accordingly for groups 1 and 2 ( P = 0.89 ) . CONCLUSION Ultrasonography has a high ability to access calculi more easily through the pyelocaliceal system with the patient in the flank position . It is convenient for urologists , and the return to the supine position is possible easily when necessary . Besides , PCNL under ultrasonography guidance and with the patient in the flank position has high success rates and limited complications ; hence , we recommend this technique as an alternative procedure for fluoroscopy-guided PCNL ABSTRACT Introduction and Hypothesis : To compare complications and outcomes of complete supine percutaneous nephrolithotomy ( csPCNL ) with ultrasound guided and fluoroscopically guided procedure . Material s and Methods : In this r and omized clinical trial study from January 2009 to September 2010 , 26 of 51 patients with renal stones underwent csPCNL with ultrasonographic guidance in all steps of the procedure ( group A ) , and the other 25 patients underwent st and ard fluoroscopically guided csPCNL ( group B ) . All of the patients underwent PCNL in the complete supine position . Statistical analysis was performed with SPSS16 software . Results : Mean BMI was 28.14 in group A and 26.31 in group B ( p=0.30 ) . The mean stone burden was 26.48 and 30.44 in groups A and B , respectively ( p=0.20 ) . The stone free rate was 88.5 % in group A and 75.5 % in group B , that was no significant ( p=0.16 ) . Overall 2 patients ( 7.7 % ) in group A and 6 patients ( 24 % ) in group B had complications ( p=0.11 ) . Mean operative time in group A was 88.46 minutes , and in group B it was 79.58 minutes ( p=0.39 ) . Mean hospital stay was 69.70 and 61.79 hours in group A and B , respectively ( p=0.22 ) . There was no visceral injury in groups . Conclusions : This r and omized study showed that totally ultrasonic had the same outcomes of fluoroscopically csPCNL . Ultrasonography can be an alternative rather than fluoroscopy in PCNL . We believe that more r and omized studies are needed to allow endourologists to use sonography rather than fluoroscopy in order to avoid exposition to radiation 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 INTRODUCTION Over the past 20 years , the use of fluoroscopy to guide urologic surgical interventions has been constantly growing . Thus , in their daily practice , urologists and other operating room ( OR ) staff are exposed to X-radiation increasingly frequently . This raises questions as to the risks they encounter and the actions needed to reduce them . OBJECTIVE Evaluate X-ray dose exposure in the members of the surgical team and determine urologist radioprotection knowledge and practice s. MATERIAL S AND METHODS A prospect i ve bicenter study was conducted within AFUF ( French urology resident association ) and in association with The French Nuclear Safety Authority/The Institute for Radiological Protection and Nuclear Safety ( ASN/IRSN ) . Radiation exposure was measured on 12 operators using dosimeters ( seven per operator ) , in staff-occupied locations in the OR using ionization chambers , and on anthropomorphic phantoms . A survey was used to gather information on radiation knowledge and safety practice s of the AFUF members . RESULTS Annual whole-body radiation doses were low ( 0.1 - 0.8 millisieverts [ mSv ] , mostly at around 0.3 mSv ) , and equivalent doses were low for the fingers ( 0.7 - 15 mSv , mostly at around 2.5 mSv ) , and low for the lens of the eye ( 0.3 - 2.3 mSv , mostly at around 0.7 mSv ) . In percutaneous nephrolithotomy , extremity doses were lower when the patient was placed in dorsal decubitus compared with ventral decubitus . Pulsed fluoroscopy reduced radiation dose exposure by a factor of 3 compared with continuous fluoroscopy with no image quality loss . Radiation safety practice s were poor : only 15 % of urologists wore dosimeters and only 5 % had been trained in the h and ling of X-ray generators . CONCLUSION In the present study , radiation exposure for urologists was low , but so was knowledge of radiation safety and optimization practice s. This absence of training for radiation safety and reduction , teamed with novel techniques involving long fluoroscopy-guided interventions , could result in unnecessarily high exposure for patients and OR personnel PURPOSE Achieving access to the pyelocaliceal system in percutaneous nephrolithotomy ( PCNL ) is routinely performed using fluoroscopic guidance . We compared ultrasonography-guided access for PCNL with conventional fluoroscopy-guided access . PATIENTS AND METHODS In a clinical trial , 100 patients with no abnormality of the upper urinary tract were selected from among c and i date s for PCNL and r and omly assigned to two 50-patient groups : ultrasonography-guided access ( group 1 ) versus fluoroscopy-guided access ( group 2 ) . In group 1 , location of the target calix was identified in the transverse and sagittal planes by real-time ultrasonography when patients were in the prone position . Puncture of the target calix was attempted with a Chiba needle attached to the side of the ultrasound probe . If access to the collecting system was achieved , the site of puncture was controlled using fluoroscopy . In group 2 , access was achieved using fluoroscopy guidance . Tract dilatation and stone extraction were the same in both groups . The mean age of patients was 40.7 + /- 12 years and 41.6 + /- 13.7 years in groups 1 and 2 , respectively ( P = 0.4 ) . The male to female ratio in groups 1 and 2 was 34/16 and 31/19 , respectively ( P = 0.5 ) . RESULTS On average , duration of access was 11 + /- 3.5 minutes and 5.5 + /- 1.7 minutes in groups 1 and 2 , respectively ( P = 0.0001 ) . Duration of radiation exposure , on average , was 0.69 + /- 0.26 minutes and 0.95 + /- 0.44 minutes in groups 1 and 2 , respectively ( P = 0.0001 ) . CONCLUSION Access for PCNL using ultrasonography guidance is an acceptable alternative to fluoroscopy and decreases radiation hazards Abstract Objective : To assess the effectiveness and advantages of ultra-mini-percutaneous nephrolithotomy ( UM-PCNL ) versus st and ard PCNL ( S-PCNL ) , as one of the most important differences between the various PCNL techniques is the size of the renal access , which contributes to the broad spectrum of complications and outcomes . Patients and methods : This clinical r and omised trial was conducted in 2016 . In all , 70 patients with renal or upper ureteric stones of 10–20 mm in diameter , who were c and i date s for PCNL , were divided equally into two groups . Group A , underwent UM-PCNL using a 9.8-F ureteroscope through a 16-F sheath ; and Group B , underwent S-PCNL using a 24-F nephroscope through a 30-F sheath . The stones were fragmented by pneumatic lithotripsy . Any perioperative complications and need for analgesia were recorded , and postoperative pain was assessed in both groups using a visual analogue scale ( VAS ) . Results : There were statistically significant differences in postoperative haemoglobin values , haemoglobin drop , transfusion rate , duration of hospitalisation and postoperative VAS pain score between the groups ( P < 0.05 ) . There were no significant differences in operation time , need for auxiliary procedures or stone-free rate . Conclusion : A minimally invasive UM-PCNL using a 9.8-F ureteroscope can play an important role in the treatment of symptomatic renal and upper ureteric stones of < 20 mm in diameter with lesser blood loss , duration of hospitalisation , need of transfusion , and postoperative pain compared with S-PCNL Background : In this study , we aim ed to explore the effect of ultrasound-guided percutaneous nephrolithotomy ( UGPN ) for the treatment in patients with kidney stones ( KS ) . Methods : We r and omly assigned 86 patients with KS to a UGPN group or a control group , each group comprising 43 patients . Patients from the UGPN group underwent UGPN whereas those from control group underwent fluoroscopic-guided percutaneous nephrolithotomy ( FGPN ) . The primary outcome included the stone-free rate . Secondary outcomes included complication rates , operative time , and length of hospitalization . Results : UGPN did not show better efficacy than the FGPN procedure in decreasing stone-free rate ( UGPN group 79.1 % vs control group 69.8 % , P = .45 ) , operative time ( UGPN group 108.4 ± 31.7 minute vs control group 113.2 ± 34.5 minute , P = .50 ) , and length of hospitalization ( UGPN group 2.7 ± 1.3 days vs control group 3.1 ± 1.5 days , P = .19 ) . Additionally , no complications , except fever ( UGPN group 4.7 % vs control group 9.3 % , P = .41 ) and hemoglobin slightly reduced ( UGPN group 7.0 % vs control group 11.6 % , P = .46 ) were noted in patients from both groups in this study . Conclusions : To summarize , we demonstrated that both UGPN and FGPN techniques showed similar efficacy and complications when used for the management of KS OBJECTIVE To examine the cost factors associated with ultrasound and fluoroscopic guidance for percutaneous nephrolithotomy ( PCNL ) and to determine which method can be performed at a lower cost per case . METHODS A cost comparison study was performed utilizing clinical data from a prospect ively maintained research data base . We included the most recent 33 consecutive ultrasound-guided PCNL cases in 2016 and the most recent 40 consecutive fluoroscopy-guided PCNL cases before the operative surgeon transitioned to ultrasound guidance in May 2014 . The total operative time and clinical outcomes were examined . Costs were extracted from the institution accounting systems and given a uniform multiplier to protect institutional financial reporting confidentiality . Comparisons were made using the Student t test and the chi-squared test . RESULTS After excluding outliers , 71 PCNL procedures were included in the analysis . Demographic data and stone characteristics were not different between ultrasound-guided and fluoroscopy-guided groups . However , the mean operative time for ultrasound-guided PCNL was significantly shorter ( 99.8 ± 27.0 vs 144.9 ± 55.1 minutes , P < .05 ) . When capital equipment costs were included , the mean total cost per case of ultrasound-guided PCNL was approximately 30 % less than fluoroscopy-guided PCNL ( simulated costs with a uniform multiplier ; $ 5258.90 ± 957.12 vs $ 7508.60 ± 1163.83 , P < .05 ) . Postoperative clinical outcomes were comparable between the 2 groups . CONCLUSION When capital costs are included , ultrasound-guided PCNL can produce comparable clinical outcomes to fluoroscopy-guided procedures at a lower cost to the institution . Shorter operative time drives significant savings with the adoption of ultrasound guidance , which may be magnified with increasing case volume . Using ultrasound imaging during PCNL may be more cost-effective compared to fluoroscopy and warrants further study BACKGROUND AND PURPOSE In percutaneous nephrolithotomy ( PCNL ) , placement of the access tract into the kidney is an important aspect of the procedure and is responsible for the steep learning curve associated with the operation . The aim of the current prospect i ve r and omized trial was to assess the duration of radiation exposure along with the safety and efficacy of PCNL done by a trainee , utilizing either ultrasonography ( US ) or fluoroscopic guidance to obtain access . PATIENTS AND METHODS Sixty-four patients with ≤3 cm renal calculi undergoing single-tract PCNL by trainee urologists ( experience of < 25 PCNL 's ) were r and omized into US- and fluoroscopic-guided access groups ( 32 in each ) . In Group 1 ( US guided ) , puncture was done using a 3.5/5 MHz US probe with a puncture attachment , whereas the triangulation technique with biplanar C-arm fluoroscopy was utilized in group 2 ( fluoroscopic guided ) . Patient demographics , stone parameters , intraoperative characteristics , fluoroscopy duration s , and postoperative outcomes were analyzed . RESULTS Both groups were comparable as far as patient and stone characteristics were concerned . The fluoroscopy exposure during the puncture phase ( T2 ) and overall ( T ) was significantly lower in the US group at 9.0±20.8 vs 43.8±34.8 , ( p<0.0001 ) and 204.3±84 vs 239.9±77.5 , ( p=0.04 ) . Six patients in group1 required fluoroscopic adjustment ( p=0.03 ) . All other intra- and postoperative parameters were similar in both the groups . CONCLUSION Both ultrasound and fluoroscopic guidance for renal access are equally safe and feasible in the h and s of a trainee urologist . Total fluoroscopy duration and exposure time during puncture were both significantly less in the ultrasound group . Expertise in fluoroscopic-guided access is essential for a novice to effectively achieve access in all possible situations |
424 | 30,343,609 | While majority of the pre- clinical and clinical studies demonstrated statistically significant effects , the clinical significance of these findings was still unclear .
Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future | Exogenous stem cell therapy ( SCT ) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors .
Mesenchymal stem cells ( MSCs ) are the primary source of stem cells used in the majority of both pre- clinical and clinical studies in stroke .
In the absence of evidence -based guidelines on the use of SCT in stroke patients , underst and ing the progress of MSC research across published studies will assist research ers and clinicians in better achieving success in translating research . | Background and Purpose — Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells ( BMSCs ) in stroke . We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke . Methods — This was a phase II , multicenter , parallel group , r and omized trial with blinded outcome assessment that included 120 patients . Patients with subacute ischemic stroke were r and omly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm . Co primary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180 . Secondary outcomes were change in infa rct volume , National Institute of Health Stroke Scale ( NIHSS ) at day 90 and 180 . Main safety outcomes were adverse events , any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days . Results — Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset . There was no significant difference between BMSCs arm and control arm in the Barthel Index score ( 63.1 versus 63.6 ; P=0.92 ) , modified Rankin scale shift analysis ( P=0.53 ) or score > 3 ( 47.5 % versus 49.2 % ; P=0.85 ) , NIHSS score ( 6.3 versus 7.0 ; P=0.53 ) , change in infa rct volume ( −11.1 versus −7.36 ; P=0.63 ) at day 180 . Adverse events were also similar in the 2 arms , and no patient showed any new area of 18fluorodeoxyglucose uptake . Conclusions — With the methods used , results of this hitherto first r and omized controlled trial indicate that intravenous infusion of BMSCs is safe , but there is no beneficial effect of treatment on stroke outcome . Clinical Trial Registration — URLs : http://ctri.nic.in/ Clinical trials and http://www . clinical trials.gov . Unique identifiers : CTRI-ROVCTRI/2008/091/0004 and NCT0150177 BACKGROUND The influence of poststroke depression on long-term survival is poorly investigated . Thus , we aim ed to evaluate the influence of major depression disorder ( MDD ) on long-term survival in the participants from The Study of Stroke Mortality and Morbidity in Adults ( EMMA Study ) in São Paulo , Brazil . METHODS We prospect ively evaluated ischemic and hemorrhagic stroke ( HS ) cases from the EMMA Study . Baseline and stroke characteristics and cardiovascular risk factors were evaluated according to MDD assessed by the Patient Health Question naire , which was applied 30 days after index event and periodically during 1-year follow-up . We performed Kaplan-Meier survival analysis , as well as crude and multiple Cox proportional hazards models . RESULTS In this subset of the EMMA Study , we evaluated 164 ( 85.9 % ) patients with ischemic stroke and 27 ( 14.1 % ) with HS . Among these , overall incidence of MDD was 25.1 % during 1 year of follow-up , regardless stroke subtype . The peak rate of major depression postacute event was beyond 1 month . We observed a lower survival rate among individuals who developed poststroke MDD than among those who did not develop this condition after 1 year of follow-up ( 85.4 % versus 96.5 % , log rank P = .006 ) . After multiple analysis , we kept a higher risk of all-cause mortality among those who developed MDD compared to participants without MDD ( hazard ratio = 4.60 , 95 % confidence interval = 1.36 - 15.55 , P = .01 ) . CONCLUSION Our findings suggest that incident MDD is a potential marker of poor prognosis 1 year after stroke Background and Purpose — Pre clinical data suggest that cell-based therapies have the potential to improve stroke outcomes . Methods — Eighteen patients with stable , chronic stroke were enrolled in a 2-year , open-label , single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow – derived mesenchymal stem cells ( SB623 ) . Results — All patients in the safety population ( N=18 ) experienced at least 1 treatment-emergent adverse event . Six patients experienced 6 serious treatment-emergent adverse events ; 2 were probably or definitely related to surgical procedure ; none were related to cell treatment . All serious treatment-emergent adverse events resolved without sequelae . There were no dose-limiting toxicities or deaths . Sixteen patients completed 12 months of follow-up at the time of this analysis . Significant improvement from baseline ( mean ) was reported for : ( 1 ) European Stroke Scale : mean increase 6.88 ( 95 % confidence interval , 3.5–10.3 ; P<0.001 ) , ( 2 ) National Institutes of Health Stroke Scale : mean decrease 2.00 ( 95 % confidence interval , −2.7 to −1.3 ; P<0.001 ) , ( 3 ) Fugl-Meyer total score : mean increase 19.20 ( 95 % confidence interval , 11.4–27.0 ; P<0.001 ) , and ( 4 ) Fugl-Meyer motor function total score : mean increase 11.40 ( 95 % confidence interval , 4.6–18.2 ; P<0.001 ) . No changes were observed in modified Rankin Scale . The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months ( P<0.001 for European Stroke Scale ) . Conclusions — In this interim report , SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01287936 PURPOSE Bone marrow stem cells ( BMSC ) were transplanted into the perilesional area in five patients bearing sequels of stroke , to evaluate the safety of the procedure and tolerance to the transplanted cells . METHODS Cells were obtained from bone marrow sample s taken from the same patient and stereotactically implanted into the targets , determined using a combination of images , and trans-operative recording of multiunit activity . The cells were implanted in several points along tracts in the perilesional region . RESULTS No important adverse events derived from surgery or transplant were observed during the one year follow-up period , or detected using a combination of tests and functional measurements applied pre- and post-surgically . In contrast , some improvements were observed regarding the neurological condition of the patients , but the small number of patients in the study does not allow any conclusive statement . CONCLUSIONS Our results demonstrate that BMSC can be safely transplanted into the brain of patients , with excellent tolerance and without complications , using the methods described here Stem cell therapy is an emerging therapeutic modality in the treatment of stroke . We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells ( NSPCs ) and mesenchymal stromal cells ( MSCs ) in patients with ischemic stroke . Eight patients were enrolled in this study . All patients had a hemisphere with infa rct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging ( MRI ) . The patients received one of the following two types of treatment : the first treatment involved four intravenous injections of MSCs at 0.5 × 106/kg body weight ; the second treatment involved one intravenous injection of MSCs at 0.5 × 106/kg weight followed by three injections of MSCs at 5 × 106/patient and NSPCs at 6 × 106/patient through the cerebellomedullary cistern . The patients ' clinical statuses were evaluated with the National Institutes of Health Stroke Scale ( NIHSS ) , the modified Rankin Scale ( mRS ) , and the Barthel index ( BI ) . Six patients were given four cell transplantations . The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2–4 days after each therapy . One patient exhibited minor dizziness . All side effects appeared within the first 2–24 h of cell transplantation , and they resolved without special treatment . There was no evidence of neurological deterioration or neurological infection . Most importantly , no tumorigenesis was found at a 2-year follow-up . The neurological functions , disability levels , and daily living abilities of the patients in this study were improved . While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function , further studies that include larger sample s , longer follow-ups , and control groups are still needed . This manuscript is published as part of the International Association of Neurorestoratology ( IANR ) special issue of Cell Transplantation The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke . Major inclusion criteria included patients with cerebral embolism , age 20–75 years , National Institute of Health Stroke Scale ( NIHSS ) score displaying improvement of ≤5 points during the first 7 days after stroke , and NIHSS score of ≥10 on day 7 after stroke . Bone marrow aspiration ( 25 or 50 mL ; N = 6 patients in each case ) was performed 7–10 days poststroke , and bone marrow mononuclear cells were administrated intravenously . Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups , respectively . No apparent adverse effects of administering bone marrow cells were observed . Compared with the lower dose , patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes . Compared with 1 month after treatment , patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment . In comparison with historical controls , patients receiving cell therapy had significantly better neurologic outcomes . Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible . Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale r and omized controlled trials using this approach Article abstract Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke . The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits , including 12 patients ( aged 44 to 75 years ) with an infa rct 6 months to 6 years previously ( stable for at least 2 months ) . Serial evaluations ( 12 to 18 months ) showed no adverse cell-related serologic or imaging-defined effects . The total European Stroke Scale score improved in six patients ( 3 to 10 points ) , with a mean improvement 2.9 points in all patients ( p = 0.046 ) . Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site . Neuronal transplantation is feasible in patients with motor infa rct ion Transplantation of human mesenchymal stem cells has been shown to reduce infa rct size and improve functional outcome in animal models of stroke . Here , we report a study design ed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells exp and ed in autologous human serum in stroke patients . We report an unblinded study on 12 patients with ischaemic grey matter , white matter and mixed lesions , in contrast to a prior study on autologous mesenchymal stem cells exp and ed in foetal calf serum that focused on grey matter lesions . Cells cultured in human serum exp and ed more rapidly than in foetal calf serum , reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis . Autologous mesenchymal stem cells were delivered intravenously 36 - 133 days post-stroke . All patients had magnetic resonance angiography to identify vascular lesions , and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after . Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients . Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores . We did not observe any central nervous system tumours , abnormal cell growths or neurological deterioration , and there was no evidence for venous thromboembolism , systemic malignancy or systemic infection in any of the patients following stem cell infusion . The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion , compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion . Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion . Mean lesion volume as assessed by magnetic resonance imaging was reduced by > 20 % at 1 week post-cell infusion . While we would emphasize that the current study was unblinded , did not assess overall function or relative functional importance of different types of deficits , and does not exclude placebo effects or a contribution of recovery as a result of the natural history of stroke , our observations provide evidence supporting the feasibility and safety of delivery of a relatively large dose of autologous mesenchymal human stem cells , cultured in autologous human serum , into human subjects with stroke and support the need for additional blinded , placebo-controlled studies on autologous mesenchymal human stem cell infusion in stroke We previously evaluated the short-term follow-up preliminary data of mesenchymal stem cells ( MSCs ) transplantation in patients with ischemic stroke . The present study was conducted to evaluate the long-term safety and efficacy of i.v . MSCs transplantation in a larger population . To accomplish this , we performed an open-label , observer-blinded clinical trial of 85 patients with severe middle cerebral artery territory infa rct . Patients were r and omly allocated to one of two groups , those who received i.v . autologous ex vivo cultured MSCs ( MSC group ) or those who did not ( control group ) , and followed for up to 5 years . Mortality of any cause , long-term side effects , and new-onset comorbidities were monitored . Of the 52 patients who were finally included in this study , 16 were the MSC group and 36 were the control group . Four ( 25 % ) patients in the MSC group and 21 ( 58.3 % ) in the control group died during the follow-up period , and the cumulative surviving portion at 260 weeks was 0.72 in the MSC group and 0.34 in the control group ( log-rank ; p = .058 ) . Significant side effects were not observed following MSC treatment . The occurrence of comorbidities including seizures and recurrent vascular episodes did not differ between groups . When compared with the control group , the follow-up modified Rankin Scale ( mRS ) score was decreased , whereas the number of patients with a mRS of 0 - 3 increased in the MSC group ( p = .046 ) . Clinical improvement in the MSC group was associated with serum levels of stromal cell-derived factor-1 and the degree of involvement of the subventricular region of the lateral ventricle . Intravenous autologous MSCs transplantation was safe for stroke patients during long-term follow-up . This therapy may improve recovery after stroke depending on the specific characteristics of the patients 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 BACKGROUND CTX0E03 is an immortalised human neural stem-cell line from which a drug product ( CTX-DP ) was developed for allogeneic therapy . Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients . METHODS We did an open-label , single-site , dose-escalation study . Men aged 60 years or older with stable disability ( National Institutes of Health Stroke Scale [ NIHSS ] score ≥6 and modified Rankin Scale score 2 - 4 ) 6 - 60 months after ischaemic stroke were implanted with single doses of 2 million , 5 million , 10 million , or 20 million cells by stereotactic ipsilateral putamen injection . Clinical and brain imaging data were collected over 2 years . The primary endpoint was safety ( adverse events and neurological change ) . This trial is registered with Clinical Trials.gov , number NCT01151124 . FINDINGS 13 men were recruited between September , 2010 , and January , 2013 , of whom 11 ( mean age 69 years , range 60 - 82 ) received CTX-DP . Median NIHSS score before implantation was 7 ( IQR 6 - 8 ) and the mean time from stroke was 29 ( SD 14 ) months . Three men had subcortical infa rcts only and seven had right-hemisphere infa rcts . No immunological or cell-related adverse events were seen . Other adverse events were related to the procedure or comorbidities . Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients . At 2 years , improvement in NIHSS score ranged from 0 to 5 ( median 2 ) points . INTERPRETATION Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function . Our observations support further investigation of CTX-DP in stroke patients . FUNDING ReNeuron Limited |
425 | 30,733,075 | Interpretation Metastatic CRC demonstrates high concordance across multiple biomarkers , suggesting that molecular testing of either the primary or liver and lung metastasis is adequate . | Background The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer ( CRC ) is well-established , requiring molecular analysis of primary or metastatic biopsies .
We aim to review concordance between primary CRC and its metastatic sites . | Summary Background In the Medical Research Council ( MRC ) COIN trial , the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to st and ard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival . Methods In this r and omised controlled trial , patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were r and omly assigned to oxaliplatin and fluoropyrimidine chemotherapy ( arm A ) , the same combination plus cetuximab ( arm B ) , or intermittent chemotherapy ( arm C ) . The choice of fluoropyrimidine therapy ( capecitabine or infused fluouroracil plus leucovorin ) was decided before r and omisation . R and omisation was done central ly ( via telephone ) by the MRC Clinical Trials Unit using minimisation . Treatment allocation was not masked . The comparison of arms A and C is described in a companion paper . Here , we present the comparison of arm A and B , for which the primary outcome was overall survival in patients with KRAS wild-type tumours . Analysis was by intention to treat . Further analyses with respect to NRAS , BRAF , and EGFR status were done . The trial is registered , IS RCT N27286448 . Findings 1630 patients were r and omly assigned to treatment groups ( 815 to st and ard therapy and 815 to addition of cetuximab ) . Tumour sample s from 1316 ( 81 % ) patients were used for somatic molecular analyses ; 565 ( 43 % ) had KRAS mutations . In patients with KRAS wild-type tumours ( arm A , n=367 ; arm B , n=362 ) , overall survival did not differ between treatment groups ( median survival 17·9 months [ IQR 10·3–29·2 ] in the control group vs 17·0 months [ 9·4–30·1 ] in the cetuximab group ; HR 1·04 , 95 % CI 0·87–1·23 , p=0·67 ) . Similarly , there was no effect on progression-free survival ( 8·6 months [ IQR 5·0–12·5 ] in the control group vs 8·6 months [ 5·1–13·8 ] in the cetuximab group ; HR 0·96 , 0·82–1·12 , p=0·60 ) . Overall response rate increased from 57 % ( n=209 ) with chemotherapy alone to 64 % ( n=232 ) with addition of cetuximab ( p=0·049 ) . Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab ( 14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours , respectively ) . Overall survival differs by somatic mutation status irrespective of treatment received : BRAF mutant , 8·8 months ( IQR 4·5–27·4 ) ; KRAS mutant , 14·4 months ( 8·5–24·0 ) ; all wild-type , 20·1 months ( 11·5–31·7 ) . Interpretation This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer . Cetuximab increases response rate , with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours . The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases can not be recommended . Funding Cancer Research UK , Cancer Research Wales , UK Medical Research Council , Merck PURPOSE Microsatellite instability ( MSI ) , TP53 mutation , and KRAS mutation status have been reported as prognostic factors in colon cancer . Most studies , however , have included heterogeneous groups of patients with respect to cancer stage . We determined the prognostic relevance of high-frequency MSI ( MSI-H ) , TP53 mutations , and KRAS mutations in a well-defined group of patients with stage III colon cancer ( N = 391 ) , r and omly assigned for adjuvant treatment with fluorouracil-based chemotherapy . METHODS Three hundred ninety-one tumor specimens were available . MSI was determined in 273 specimens , and mutation analyses of TP53 and KRAS were performed in 220 and 205 specimens , respectively . RESULTS In a univariate analysis , MSI-H ( 44 of 273 ; 16 % ) was associated with a longer disease-free survival ( DFS ; P = .038 ) , but in a multivariate model adjusting for nodal involvement , histology , invasion , and grade of tumor , the association of MSI status with DFS did no longer reach statistical significance , though the risk estimate for microsatellite stability versus MSI-H tumors did not change much . Mutant TP53 , found in 116 ( 53 % ) of 220 tumors , was associated with a shorter DFS , both in univariate ( P = .009 ) and multivariate analyses ( P = .018 ) , whereas KRAS mutations ( 58 of 205 ; 28 % ) did not show any prognostic significance . CONCLUSION Both mutant TP53 and MSI-H seem to be prognostic indicators for disease-free survival , but only TP53 retains statistical significance after adjusting for clinical heterogeneity . Thus , in adjuvantly treated patients with stage III colon cancer , presence or absence of a TP53 mutation should be considered as a better predictor for DFS than MSI status |
426 | 28,185,257 | AUTHORS ' CONCLUSIONS The available evidence suggests that system change interventions for smoking cessation may not be effective in achieving increased cessation rates , but have been shown to improve process outcomes , such as documentation of smoking status , provision of cessation counselling and referral to smoking cessation services . | BACKGROUND System change interventions for smoking cessation are policies and practice s design ed by organizations to integrate the identification of smokers and the subsequent offering of evidence -based nicotine dependence treatments into usual care .
Such strategies have the potential to improve the provision of smoking cessation support in healthcare setting s , and cessation outcomes among those who use them .
OBJECTIVES To assess the effectiveness of system change interventions within healthcare setting s , for increasing smoking cessation or the provision of smoking cessation care , or both . | OBJECTIVES This study assessed the effectiveness of a smoking cessation program for women in public health clinics , controlling for reported exposures to 4 common intervention components ( provider advice , booklet , video segment , posters ) among smokers in the control group . METHODS After a baseline control period , 10 pair-matched clinics were r and omly assigned to study groups . A total of 1042 smokers in the combined baseline and control groups and 454 smokers in the intervention group completed a preintervention question naire and a postintervention telephone interview 5 to 8 weeks later . Eight smoking outcomes , including quitting , were analyzed for the effect of reported exposure to intervention components , experimental program , and clinic service . RESULTS Greater exposure to intervention components , being in the experimental program , and being seen in prenatal clinics independently improved smoking outcomes . CONCLUSIONS The number of interventions reported by smokers in the control group ranged from none to 4 and varied across clinic services . The experimental program we tested produced better outcomes than the minimal smoking cessation interventions already existing in the control clinics , after we controlled for whether smokers were or were not exposed to these interventions BACKGROUND Because smoking has a profound impact on socioeconomic disparities in illness and death , it is crucial that vulnerable population s of smokers be targeted with treatment . The U.S. Public Health Service recommends that all patients be asked about their smoking at every visit and that smokers be given brief advice to quit and referred to treatment . PURPOSE Initiatives to facilitate these practice s include the 5A 's ( ask , advise , assess , assist , arrange ) and Ask-Advise-Refer ( AAR ) . Unfortunately , primary care referrals are low , and most smokers referred fail to enroll . This study evaluated the efficacy of the Ask-Advise-Connect ( AAC ) approach to linking smokers with treatment in a large , safety net public healthcare system . DESIGN The study design was a pair-matched group-r and omized trial with two treatment arms . SETTING / PARTICIPANTS Ten safety net clinics in Houston TX . INTERVENTION Clinics were r and omized to AAC ( n=5 ; intervention ) or AAR ( n=5 ; control ) . Licensed vocational nurses ( LVNs ) were trained to assess and record the smoking status of all patients at all visits in the electronic health record . Smokers were given brief advice to quit . In AAC , the names and phone numbers of smokers who agreed to be connected were sent electronically to the Texas quitline daily , and patients were proactively called by the quitline within 48 hours . In AAR , smokers were offered a quitline referral card and encouraged to call on their own . Data were collected between June 2010 and March 2012 and analyzed in 2012 . MAIN OUTCOME MEASURES The primary outcome was impact , defined here as the proportion of identified smokers that enrolled in treatment . RESULTS The impact ( proportion of identified smokers who enrolled in treatment ) of AAC ( 14.7 % ) was significantly greater than the impact of AAR ( 0.5 % ) , t(4)=14.61 , p=0.0001 , OR=32.10 ( 95 % CI=16.60 , 62.06 ) . CONCLUSIONS The AAC approach to aiding smoking cessation has tremendous potential to reduce tobacco-related health disparities Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly Background Argentina and Uruguay are among the countries with the highest proportion of pregnant women who smoke . The implementation of an effective smoking cessation intervention would have a significant impact on the health of mothers and infants . The “ 5 A ’s ” ( Ask , Advise , Assess , Assist , Arrange ) is a strategy consisting of a brief cessation counseling session of 5–15 minutes delivered by a trained provider . The “ 5 A ’s ” is considered the st and ard of care worldwide ; however , it is under used in Argentina and Uruguay . Methods We will conduct a two-arm , parallel cluster r and omized controlled trial of an implementation intervention in 20 prenatal care setting s in Argentina and Uruguay . Prenatal care setting s will be r and omly allocated to either an intervention or a control group after a baseline data collection period . Midwives ’ facilitators in the 10 intervention prenatal clinics ( clusters ) will be identified and trained to deliver the “ 5 A ’s ” to pregnant women and will then disseminate and implement the program . The 10 clusters in the control group will continue with their st and ard in-service activities . The intervention will be tailored by formative research to be readily applicable to local prenatal care services at maternity hospitals and acceptable to local pregnant women and health providers . Our primary hypothesis is that the intervention is feasible in prenatal clinics in Argentina and Uruguay and will increase the frequency of women receiving tobacco use cessation counseling during pregnancy in the intervention clinics compared to the control clinics . Our secondary hypotheses are that the intervention will decrease the frequency of women who smoke by the end of pregnancy , and that the intervention will increase the attitudes and readiness of midwives towards providing counseling to women in the intervention clinics compared to the control clinics . Trial registration Clinical Trials.gov . Identifier : Background Extended smoking cessation follow-up after hospital discharge significantly increases abstinence . Hospital smoke-free policies create a period of ‘ forced abstinence ’ for smokers , thus providing an opportunity to integrate tobacco dependence treatment , and to support post-discharge maintenance of hospital-acquired abstinence . This study is funded by the National Heart , Lung , and Blood Institute ( 1U01HL1053231 ) . Methods / Design The Inpatient Technology-Supported Assisted Referral study is a multi-center , r and omized clinical effectiveness trial being conducted at Kaiser Permanente Northwest ( KPNW ) and at Oregon Health & Science University ( OHSU ) hospitals in Portl and , Oregon . The study assesses the effectiveness and cost-effectiveness of linking a practical inpatient assisted referral to outpatient cessation services plus interactive voice recognition ( AR + IVR ) follow-up calls , compared to usual care inpatient counseling ( UC ) . In November 2011 , we began recruiting 900 hospital patients age ≥18 years who smoked ≥1 cigarettes in the past 30 days , willing to remain abstinent postdischarge , have a working phone , live within 50 miles of the hospital , speak English , and have no health-related barriers to participation . Each site will r and omize 450 patients to AR + IVR or UC using a 2:1 assignment strategy . Participants in the AR + IVR arm will receive a brief inpatient cessation consult plus a referral to available outpatient cessation programs and medications , and four IVR follow-up calls over seven weeks postdischarge . Participants do not have to accept the referral . At KPNW , UC participants will receive brief inpatient counseling and encouragement to self-enroll in available outpatient services . The primary outcome is self-reported thirty-day smoking abstinence at six months postr and omization for AR + IVR participants compared to usual care . Additional outcomes include self-reported and biochemically confirmed seven-day abstinence at six months , self-reported seven-day , thirty-day , and continuous abstinence at twelve months , intervention dose response at six and twelve months for AR + IVR recipients , incremental cost-effectiveness of AR + IVR intervention compared to usual care at six and twelve months , and health-care utilization and expenditures at twelve months for AR + IVR recipients compared to UC . Discussion This study will provide important evidence for the effectiveness and cost-effectiveness of linking hospital-based tobacco treatment specialists ’ services with discharge follow-up care . Trial Registration Clinical Trials.gov : AIMS Two methods of dissemination ( simple and intensive ) were used to disseminate a smoking cessation programme to doctors and midwives working in antenatal clinics . This paper describes the differential uptake of the smoking cessation programme by doctors and midwives . It investigates whether the number of smoking cessation interventions used differ due to the type of dissemination . It also examines the frequency with which doctors and midwives provide smoking cessation interventions after dissemination . DESIGN Clinics were r and omized to the method of dissemination ( simple or intensive ) . Pre-post test design was used to examine the relationship between dissemination method and professional status at baseline and follow-up . A baseline survey collected data on the use of smoking cessation intervention in the clinics prior to dissemination . A follow-up survey was conducted 18 months after the dissemination . SETTING Twenty-three public hospital antenatal clinics in NSW . PARTICIPANTS All clinical staff ( midwives and doctors ) working in the clinic during the 1 - 2-week survey period prior to dissemination and 18 months after the dissemination were asked to participate . The response rate was 63 % ( 223 ) at baseline and 64 % ( 182 ) at follow-up . Only 48 % of midwives and doctors at follow-up were working in the original clinic . MEASURES The proportion of clinicians who initially adopted the programme ; the proportion of clinicians who had used one or more programme components in the last week ) ; the number of types of smoking cessation intervention provided ( maximum = 13 ) , and the estimated proportion of clients offered smoking cessation intervention . FINDINGS More midwives than doctors " ever used " the programme ( 76 % vs. 25 % ) and continued to implement ( 58 % vs. 22 % ) the programme 18 months after dissemination . Both midwives and doctors increased the number of types of smoking cessation intervention offered at follow-up compared to baseline ( mean difference 2.8 ) . Midwives provided more smoking cessation interventions than doctors at baseline ( mean difference 0.9 ) and at follow-up ( 1.6 ) , regardless of method used to disseminate the programme . Midwives ' mean estimates of the proportion of clients offered interventions were greater than doctors ' ( midwives ' 59 % vs. doctors ' 35 % ) at follow-up . CONCLUSION The dissemination of a smoking cessation programme increased the level of smoking cessation interventions used by doctors and midwives . Doctors and midwives differ in their uptake of smoking cessation programmes . This information can be used to plan programme dissemination strategies in the future 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 STUDY OBJECTIVE To test whether physicians who receive a continuing education program ( " Quit for Life " ) about how to counsel smokers to quit would counsel smokers more effectively and have higher rates of long-term smoking cessation among their patients who smoke . DESIGN R and omized trial with blinded assessment of principal outcomes . SETTING Four health maintenance organization medical centers in northern California . SUBJECTS Eighty-one internists assigned by blinded r and omization to receive training ( 40 ) or serve as controls ( 41 ) . Consecutive sample s of smokers visiting each physician ( mean , 25.6 patients per experimental and 25.2 per control physician ) . INTERVENTIONS Internists received 3 hours of training about how to help smokers quit . Physicians and their office staff also were given self-help booklets to distribute free to smokers and were urged to use a system of stickers on charts to remind physicians to counsel smokers about quitting . MEASUREMENTS AND MAIN RESULTS On the basis of telephone interviews with patients after visiting the physician , we determined that internists who attended the Quit for Life program discussed smoking with more patients who smoked , spent more time counseling them about smoking , helped more patients set date s to quit smoking , gave out more self-help booklets , and made more follow-up appointments to discuss smoking than did internists in the control group . One year later , the rate of biochemically confirmed , long-term ( greater than or equal to 9 months ) abstinence from smoking was 1 % higher among all patients of trained internists than among patients of controls ( 95 % CI , -0.1 % to + 2.3 % ) , and 2.2 % ( + 0.2 % to + 4.3 % ) higher among the patients who most wanted to quit smoking . CONCLUSIONS This continuing education program substantially changed the way physicians counseled smokers . As a result , a few more patients who wanted to quit smoking achieved long-term abstinence OBJECTIVES Tobacco use adversely affects oral health . Clinical guidelines recommend that oral health professionals promote tobacco abstinence and provide patients who use tobacco with brief tobacco use cessation counselling . Research shows that these guidelines are seldom implemented successfully . This study aim ed to evaluate two interventions to enhance tobacco use prevention and cessation ( TUPAC ) counselling among oral health professionals in Finl and . METHODS We used a cluster-r and omized community trial to test educational and fee-for-service interventions in enhancing TUPAC counselling among a sample of dentists ( n=73 ) and dental hygienists ( n=22 ) in Finl and . Educational intervention consisted of 1 day of training , including lectures , interactive sessions , multimedia demonstrations and a role play session with st and ard patient cases . Fee-for-service intervention consisted of monetary compensation for providing tobacco use prevention or cessation counselling . TUPAC counselling procedures provided were reported and measured using an electronic dental records system . In data analysis , intent-to-treat principles were followed at both individual and cluster levels . Descriptive analysis included chi-square and t-tests . A general linear model for repeated measures was used to compare the outcome measures by intervention group . RESULTS Of 95 providers , 73 participated ( 76.8 % ) . In preventive counselling , there was no statistically significant time effect or group-by-time interaction . In cessation counselling , statistically significant group-by-time interaction was found after a 6-month follow-up ( F=2.31 ; P=0.007 ) , indicating that counselling activity increased significantly in intervention groups . On average , dental hygienists showed greater activity in tobacco prevention ( F=12.13 ; P=0.001 ) and cessation counselling ( F=30.19 ; P<0.001 ) than did dentists . In addition , cessation counselling showed a statistically significant provider-by-group-by-time interaction ( F=5.95 ; P<0.001 ) , indicating that interventions to enhance cessation counselling were more effective among dental hygienists . CONCLUSIONS Educational intervention yielded positive short-term effects on cessation counselling , but not on preventive counselling . Adding a fee-for-service to education failed to significantly improve TUPAC counselling performance . Other approaches than monetary incentives may be needed to enhance the effectiveness of educational intervention . Further studies with focus on how to achieve long-term changes in TUPAC counselling activity among oral health professionals are needed Project QUIT ( Quality in Tobacco Control ) examines the implementation of the Agency for Health Care Policy and Research ( AHCPR ) guideline on smoking cessation at Allina Health System (AHS).1 As this is an ongoing project , the data presented is preliminary . It has been established that the identification of smokers and brief advice to quit constitute an effective smoking cessation intervention for patient population s. Currently , providers around the country only follow guideline recommendations to identify patients ’ tobacco use status and to provide brief advice to quit between 40–60 % of the time.2 AHS is the largest healthcare system in Minnesota and consists of an administrative unit , the “ health plan ” and a care-oriented “ delivery ” arm . AHS ’s health plan ( Medica Health Plans ) currently enrols approximately 1.1 million individuals and entails a network of more than 9000 providers . On its “ delivery side ” Allina includes 20 owned or managed hospitals , and a large group practice consisting of 57 mostly primary care clinics , in addition to home healthcare services , nursing homes , transportation services , and other business units . These delivery sites contract with a multitude of payers including AHS ’s own health plan . Overall , AHS touches the lives of approximately 2.5 million individuals each year . The objectives of our ongoing project are twofold : ( a ) to determine if clinic practice patterns change as a result of an intervention aim ing to implement the AHCPR guideline on smoking cessation , and ( b ) to determine if patients seen in clinics exposed to this intervention are more likely to quit smoking . The preliminary data associated with the first objective are presented here . # # # SAMPLE This study was launched within AHS ’s group practice organisation , Objective The primary care visit represents an important venue for intervening with a large population of smokers . However , physician adherence to the Smoking Cessation Clinical Guideline ( 5As ) remains low . We evaluated the effectiveness of a computer-tailored intervention design ed to increase smoking cessation counseling by primary care physicians . Methods Physicians and their patients were r and omized to either intervention or control conditions . In addition to brief smoking cessation training , intervention physicians and patients received a one-page report that characterized the patients ’ smoking habit and history and offered tailored recommendations . Physician performance of the 5As was assessed via patient exit interviews . Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews . Intervention effects were tested in a sample of 70 physicians and 518 of their patients . Results were analyzed via generalized and mixed linear modeling controlling for clustering . Measurements and Main Results Intervention physicians exceeded controls on “ Assess ” ( OR 5.06 ; 95 % CI 3.22 , 7.95 ) , “ Advise ” ( OR 2.79 ; 95 % CI 1.70 , 4.59 ) , “ Assist – set goals ” ( OR 4.31 ; 95 % CI 2.59 , 7.16 ) , “ Assist – provide written material s ” ( OR 5.14 ; 95 % CI 2.60 , 10.14 ) , “ Assist – provide referral ” ( OR 6.48 ; 95 % CI 3.11 , 13.49 ) , “ Assist – discuss medication ” ( OR 4.72;95 % CI 2.90 , 7.68 ) , and “ Arrange ” ( OR 8.14 ; 95 % CI 3.98 , 16.68 ) , all p values being < 0.0001 . Intervention patients were 1.77 ( CI 0.94 , 3.34,p = 0.078 ) times more likely than controls to be abstinent ( 12 versus 8 % ) , a difference that approached , but did not reach statistical significance , and surpassed controls on number of days quit ( 18.4 versus 12.2 , p < .05 ) but not on number of quit attempts . Conclusions The use of a brief computer-tailored report improved physicians ’ implementation of the 5As and had a modest effect on patients ’ smoking behaviors 6 months postintervention Background Although dental care setting s provide an exceptional opportunity to reach smokers and provide brief cessation advice and treatment to reduce oral and other tobacco-related health conditions , dental care providers demonstrate limited adherence to evidence -based guidelines for treatment of tobacco use and dependence . Methods / Design Guided by a multi-level , conceptual framework that emphasizes changes in provider beliefs and organizational characteristics as drivers of improvement in tobacco treatment delivery , the current protocol will use a cluster , r and omized design and multiple data sources ( patient exit interviews , provider surveys , site observations , chart audits , and semi-structured provider interviews ) to study the process of implementing clinical practice guidelines for treating tobacco dependence in 18 public dental care clinics in New York City . The specific aims of this comparative-effectiveness research trial are to : compare the effectiveness of three promising strategies for implementation of tobacco use treatment guidelines —staff training and current best practice s ( CBP ) , CBP + provider performance feedback ( PF ) , and CBP + PF + provider reimbursement for delivery of tobacco cessation treatment ( pay-for-performance , or P4P ) ; examine potential theory-driven mechanisms hypothesized to explain the comparative effectiveness of three strategies for implementation ; and identify baseline organizational factors that influence the implementation of evidence -based tobacco use treatment practice s in dental clinics . The primary outcome is change in providers ’ tobacco treatment practice s and the secondary outcomes are cost per quit , use of tobacco cessation treatments , quit attempts , and smoking abstinence . Discussion We hypothesize that the value of these promising implementation strategies is additive and that incorporating all three strategies ( CBP , PF , and P4P ) will be superior to CBP alone and CBP + PF in improving delivery of cessation assistance to smokers . The findings will improve knowledge pertinent to the implementation , dissemination , and sustained utilization of evidence -based tobacco use treatment in dental practice s . Trial registration NCT01615237 We report results from an experimental study that tested the effectiveness of dissemination interventions to improve implementation of smoking cessation guidelines in maternal and child public health clinics . We additionally examine individual clinic results for context ual explanations not apparent from the experimental findings alone . Twelve clinics in Illinois were r and omized to three dissemination strategies : ( i ) core dissemination ( provision of the 2000 Public Health System Clinical Practice Guideline and a tested smoking cessation program , including program supplies and training ) , ( ii ) core dissemination and access to telephone counseling and ( iii ) core dissemination , telephone counseling access and outreach visits to clinics . Implementation outcomes were post-dissemination improvements over baseline in the percent of smokers reporting receipt/exposure to ( i ) provider advice , ( ii ) self-help booklet , ( iii ) videos , ( iv ) posters and ( v ) an adjunct intervention . Results showed significant increases in the percent of smokers receiving a booklet ( overall ) and an adjunct intervention ( Groups 2 and 3 ) . There were no increases in smoker-reported provider advice or videos and poster exposure . Examination of individual clinic findings showed that seven clinics accounted for all the experimental effectiveness . Smoker-reported provider advice to quit also increased in these clinics . Type of clinic and the absence of disruptive events distinguished clinics with and without effective dissemination outcomes Objectives To investigate the effectiveness of the systematic default provision of smoking cessation support to all adult smokers admitted to hospital , relative to usual care . Design Open , cluster r and omised controlled trial . Setting Acute medical wards in one large teaching hospital in the United Kingdom . Participants 264 patients r and omised to intervention and 229 to usual care ; primary outcome data were available at four weeks for 260 and 224 patients , respectively . All adult smokers and recent ex-smokers able to give informed consent were eligible for entry into the study . Interventions The intervention comprised systematic smoking ascertainment and default provision of behavioural support and cessation pharmacotherapy for the duration of the hospital stay for all smokers and recent ex-smokers , with follow-up and referral to community services after discharge . Usual care comprised cessation support delivered at the initiative and discretion of clinical staff . All staff and patients were aware of group assignment . Main outcome measures Smoking cessation at four weeks , vali date d by measuring exhaled carbon monoxide . Secondary outcomes were uptake of inpatient behavioural support , use of cessation pharmacotherapy , referral to and uptake of community support after discharge , and vali date d smoking cessation at six months . Participants lost to follow-up were assumed to have reverted to smoking . Results All patients in the intervention group received at least brief advice to quit smoking , compared to 106 ( 46 % ) patients in the usual care group . Cessation at four weeks was achieved by 38 % ( n=98 ) of intervention patients and 17 % ( n=37 ) of usual care patients ( adjusted odds ratio 2.10 ( 95 % confidence interval 0.96 to 4.61 ) , P=0.06 , number of patients needed to treat 8) . Uptake of inpatient behavioural support , use of pharmacotherapy , and referral to and uptake of community support after discharge were all substantially and statistically significantly higher in the intervention group than in the usual care group . Cessation at six months was achieved by 19 % ( n=47 ) of intervention and 9 % ( n=19 ) of usual care patients , although this difference was not significant ( adjusted odds ratio 1.53 ( 95 % confidence interval 0.60 to 3.91 ) ; P=0.37 ) . Conclusions Substantial improvements in smoking cessation among smokers admitted to hospital can be achieved by systematic ascertainment and delivery of cessation support in secondary care . Trial registration International St and ard R and omised Controlled Trial Number IS RCT N25441641 BACKGROUND The Agency for Healthcare Research and Quality ( AHRQ ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit . METHODS We conducted a r and omized , controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin ( four test sites , four control sites ) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period ( June 16 , 1999 , to June 20 , 2000 ) or the intervention period ( from June 21 , 2000 , to May 3 , 2001 ) . After collecting baseline data , staff at test sites implemented the intervention over a 2-month period . The intervention included a tutorial for intake clinicians , group and individual performance feedback for intake clinicians , use of a modified vital signs stamp , an offer of free nicotine replacement therapy , and proactive telephone counseling . Staff at control sites received only general information about the AHRQ Guideline . Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessment s. Hierarchical logistic regression models were used to estimate the odds ratios ( ORs ) for treatment assignment after adjustment for patient characteristics . All statistical tests were two-sided . RESULTS There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period . Among participants treated during the intervention period , those at test sites were more likely than those at control sites to report being abstinent at the 2-month ( 16.4 % versus 5.8 % ; adjusted OR = 3.3 , 95 % confidence interval [ CI ] = 1.9 to 5.6 ; P<.001 ) and 6-month ( 15.4 % versus 9.8 % ; adjusted OR = 1.7 , 95 % CI = 1.2 to 2.6 ; P = .009 ) follow-up assessment s and to report continuous abstinence , that is , abstinence at both 2 and 6 months ( 10.9 % versus 3.8 % ; adjusted OR = 3.4 , 95 % CI = 1.8 to 6.3 ; P<.001 ) . CONCLUSION Implementation of a guideline -based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers CONTEXT Routine treatment of smokers by physicians is a national health objective for the year 2000 , a quality measure for health care plans , and the subject of evidence -based clinical guidelines . There are few national data on how physicians ' practice s compare with these st and ards . OBJECTIVE To assess recent trends in the treatment of smokers by US physicians in ambulatory care and to determine whether physicians ' practice s meet current st and ards . DESIGN Analysis of 1991 - 1995 data from the National Ambulatory Medical Care Survey , an annual survey of a r and om sample of US office-based physicians . SETTING Physicians ' offices . PATIENTS A total of 3254 physicians recorded data on 145716 adult patient visits . MAIN OUTCOME MEASURES The proportion of visits at which physicians ( 1 ) identified a patient 's smoking status , ( 2 ) counseled a smoker to quit , and ( 3 ) used nicotine replacement therapy . RESULTS Smoking counseling by physicians increased from 16 % of smokers ' visits in 1991 to 29 % in 1993 ( P<.001 ) and then decreased to 21 % of smokers ' visits in 1995 ( P<.001 ) . Nicotine replacement therapy use followed a similar pattern , increasing from 0.4 % of smokers ' visits in 1991 to 2.2 % in 1993 ( P<.001 ) and decreasing to 1.3 % of smokers ' visits in 1995 ( P=.007 ) . Physicians identified patients ' smoking status at 67 % of all visits in 1991 ; this proportion did not increase over time . Primary care physicians were more likely to provide treatment to smokers than were specialists . All physicians were more likely to treat patients with smoking-related diagnoses . CONCLUSIONS US physicians ' treatment of smokers improved little in the first half of the 1990s , although a transient peak in counseling and nicotine replacement use occurred in 1993 after the introduction of the nicotine patch . Physicians ' practice s fell far short of national health objectives and practice guidelines . In particular , patient visits for diagnoses not related to smoking represent important missed opportunities for intervention OBJECTIVES To test the feasibility of implementing ask-advise-refer ( AAR ) tobacco cessation counseling approach in community chain pharmacies serving low socioeconomic areas and to assess the effectiveness of a multimodal intervention on short-term implementation of AAR . DESIGN R and omized controlled trial . SETTING South- central Wisconsin from July 2008 through March 2009 . PARTICIPANTS Pharmacists and technicians from 16 community chain pharmacies . INTERVENTION Training to implement AAR , workflow integration recommendations , tobacco cessation poster to create awareness , and a support visit . MAIN OUTCOME MEASURES Number of pharmacy patrons asked about tobacco use , number of tobacco users advised to quit , number of tobacco users enrolled in the quit line , and number of quit line cards given . RESULTS As hypothesized , the multimodal intervention significantly predicted the number of patrons asked to quit ( estimate 4.84 , incidence rate ratio 127.2 , P < 0.001 ) , number of tobacco users advised to quit ( 2.12 , 8.33 , P < 0.01 ) , number of tobacco users enrolled in the quit line ( 2.31 , 10.13 , P < 0.001 ) , and number of quit line cards given ( 1.04 , 2.82 , P < 0.05 ) . CONCLUSION This trial demonstrates the feasibility of implementing AAR in routine community pharmacy practice . This trial also supports the short-term effectiveness of the multimodal intervention in facilitating AAR in partnership with other public health systems . More research is needed to evaluate the generalizability , effectiveness , and sustainability of AAR , including factors influencing adoption and the impact on cessation OBJECTIVE To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation . STUDY DESIGN A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care . METHODS The study was performed at 18 Veterans Health Administration ( VA ) sites in California . Participants were VA patients receiving primary care . We r and omly allocated 10 of 18 sites to receive the Telephone Care Coordination Program , which included simple 2-click referral , proactive care coordination , medication management , and 5 follow-up telephone calls . Each patient received a 30- to 45-minute counseling session from the California Smokers ' Helpline . Patients at control sites received usual care . RESULTS During 10 months , we received 2965 referrals . We were unable to reach 1156 patients ( 39 % ) , despite at least 3 attempts . We excluded 73 patients ( 3 % ) , and 391 patients ( 13 % ) were not interested . We connected the remaining 1345 patients ( 45 % ) to the Helpline . At 6-month followup , 335 patients ( 11 % of all referrals and 25 % of participating patients ) were abstinent . Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites ( 15.6 vs 0.7 in the prior month ) . CONCLUSIONS The program generated a large number of referrals ; almost half of the patients referred were connected with the Helpline . Long-term abstinence was excellent . These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination BACKGROUND Evidence suggests that preoperative clinics , like other hospital outpatient clinics and inpatient wards , fail to systematic ally provide smoking cessation care to patients having planned surgery . METHODS The aim of the study was to assess the efficacy , acceptability , and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic . Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study . One hundred twenty-four patients were r and omly assigned to an experimental group and 86 patients to a usual cessation care group . A multifaceted intervention was developed that included the use of opinion leaders , consensus processes , computer-delivered cessation care , computer-generated prompts for care provision by clinic staff , staff training , and performance feedback . RESULTS Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material . Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing ( 79 % vs. 47 % ; P < 0.01 ) and anaesthetic ( 60 % vs. 39 % ; P < 0.01 ) staff . Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy ( NRT ) ( 82 % vs. 8 % ; P < 0.01 ) and be prescribed postoperative NRT ( 86 % vs. 0 % ; P < 0.01 ) . The multifaceted intervention was found to be acceptable by staff . CONCLUSION A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients Background : The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users . Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice . Objectives : The Guideline Implementation for Tobacco ( GIFT ) study tested an organizational intervention to improve Guideline implementation . Research Design : GIFT r and omized 20 Veterans Affairs medical centers to intervention or control conditions . We trained prime movers at each site to improve identification of smoking status , promote primary care interventions and increase availability of smoking cessation medications . Sites and patients were evaluated before and after intervention . Subjects : GIFT included 20 Veterans Affairs medical centers and 5678 subjects . Measures : Data regarding smoking status , delivery of treatment , medication use , and smoking cessation were collected from participant surveys , medical record review , survey of site leaders , and Pharmacy Benefits Management . Results : The intervention did not increase participant report of being asked about smoking status or receipt of counseling . It did increase the rate of identification of smoking status in the medical record ( P = 0.0001 ) but did not increase the rate of counseling to stop smoking . Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications . Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites ( odds ratio = 6.89 , P < 0.0001 ) ; however , only a small minority of smokers received medication even after the intervention . There was no difference in smoking cessation rates between participants at the intervention and treatment sites . Conclusions : We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population 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 OBJECTIVES The objectives of this study are to design and implement a system-level tobacco-control intervention in a large prepaid dental group practice and assess effects on staff performance measures and patient satisfaction . METHODS We matched 14 dental facilities on size , socioeconomic status , smoking rate , and periodontal status , and then r and omly assigned them to intervention or usual-care control . We trained intervention staff in an " Assisted Referral " team approach for assessing tobacco use , providing tailored advice and brief counseling , and encouraging smokers to talk by telephone with a specially trained tobacco counselor . Patients could call from the office or ask that the counselor call them later . Telephone counselors helped patients explore motivations and barriers for quitting ; review available cessation-support strategies , programs , and medications ; and identify next steps . RESULTS During the 14-month study period , 66,516 members had annual- or new-patient examinations . Both intervention and control sites had high rates of tobacco assessment ( 97 percent ) and advice ( 93 percent ) . Intervention patients were more likely than controls ( 69 percent versus 3 percent , P < 0.01 ) to receive additional chair-side tobacco counseling and assistance , and 11 percent agreed to receive additional telephone counseling . Intervention patients were more satisfied than controls with the dental team 's tobacco-control efforts ( P < 0.03 ) . Referral rates varied substantially for different staff . CONCLUSIONS The Assisted Referral approach was successfully integrated into routine dental care , was well received by patients , and result ed in increased patient satisfaction . Because free telephone-based tobacco counseling is now available nationwide , the approach may be a practical strategy for most dental-care setting AIMS To evaluate the effectiveness of a pharmacist-led multi-component smoking cessation programme ( GIVE UP FOR GOOD ) compared with usual care in hospitalized smokers . DESIGN R and omized , assessor-blinded , parallel-group trial . SETTING Three tertiary public hospitals in Australia . PARTICIPANTS A total of 600 adult in-patient smokers [ mean ± st and ard deviation ( SD ) , age 51 ± 14 years ; 64 % male ] available for 12 months follow-up . INTERVENTIONS Multi-component hospital pharmacist-led behavioural counselling and /or pharmacotherapy provided during hospital stay , on discharge and 1 month post-discharge , with further support involving community health professionals ( n = 300 ) . Usual care comprised routine care provided by hospitals ( n = 300 ) . MEASUREMENTS Two primary end-points were tested using intention-to-treat analysis : carbon monoxide (CO)-vali date d 1-month sustained abstinence at 6-month follow-up and verified 6-month sustained abstinence at 12-month follow-up . Smoking status and pharmacotherapy usage were assessed at baseline , discharge , 1 , 6 and 12 months . FINDINGS Sustained abstinence rates for intervention and control groups were not significantly different at both 6 months [ 11.6 % ( 34 of 294 ) versus 12.6 % ( 37 of 294 ) ; odds ratio ( OR ) = 0.91 , 95 % confidence interval ( CI ) = 0.55 - 1.50 ] and 12 months [ 11.6 % ( 34 of 292 ) versus 11.2 % ( 33 of 294 ) ; OR = 1.04 , 95 % CI = 0.63 - 1.73 ] . Secondary end-points , self-reported continuous abstinence at 6 and 12 months , also agreed with the primary end-points . Use of pharmacotherapy was higher in the intervention group , both during hospital stay [ 52.3 % ( 157 of 300 ) versus 42.7 % ( 128 of 300 ) ; P = 0.016 ] and after discharge [ 59.6 % ( 174 of 292 ) versus 43.5 % ( 128 of 294 ) ; P < 0.001 ] . CONCLUSIONS A pharmacist-led multi-component smoking cessation intervention provided during hospital stay did not improve sustained abstinence rates at either 6 or 12 months compared with routine hospital care Background The provision of smoking cessation support in Australian drug and alcohol treatment services is sub-optimal . This study examines the cost-effectiveness of an organisational change intervention to reduce smoking amongst clients attending drug and alcohol treatment services . Methods / design A cluster-r and omised controlled trial will be conducted with drug and alcohol treatment centres as the unit of r and omisation . Biochemically verified ( carbon monoxide by breath analysis ) client 7-day-point prevalence of smoking cessation at 6 weeks will be the primary outcome measure . The study will be conducted in 33 drug and alcohol treatment services in four mainl and states and territories of Australia : New South Wales , Australian Capital Territory , Queensl and , and South Australia . Eligible services are those with ongoing client contact and that include pharmacotherapy services , withdrawal management services , residential rehabilitation , counselling services , and case management services . Eligible clients are those aged over 16 years who are attending their first of a number of expected visits , are self-reported current smokers , proficient in the English language , and do not have severe untreated mental illness as identified by the service staff . Control services will continue to provide usual care to the clients . Intervention group services will receive an organisational change intervention , including assistance in developing smoke-free policies , nomination of champions , staff training and educational client and service re sources , and free nicotine replacement therapy in order to integrate smoking cessation support as part of usual client care . Discussion If effective , the organisational change intervention has clear potential for implementation as part of the st and ard care in drug and alcohol treatment centres . Trial registration Australian and New Zeal and Clinical Trials Registry , ACTRN12615000204549 . Registered on 3 March 2015 INTRODUCTION Smoking prevalence is 49 % among Medicaid enrollees in Ohio . The objective of this pilot project was to test a comprehensive tobacco dependence treatment program targeting rural Medicaid-enrolled smokers for both physician-level and smoker-level outcomes . METHODS Using a group-r and omized trial design , intervention group physicians ( n = 4 ) were exposed to systems-level changes in their clinics , and smokers in these clinics were offered 12 weeks of telephone cessation counseling . Control group physicians ( n = 4 ) were given the clinician 's version of the U.S. Public Health Serivce ( USPHS ) Clinical Practice Guideline , and smokers in these clinics were given information about the Ohio Tobacco Quitline . Physician-level and smoker-level outcomes were assessed at 1 week and 3 months , respectively . Costs per quit were estimated . RESULTS A total of 214 Medicaid smokers were enrolled . At 1 week , there were no reported differences in rates of being asked about tobacco use ( 68 % intervention , 58 % control ) or advised to quit ( 69 % intervention , 63 % control ) . However , 30 % of intervention and 56 % of control smokers reported receiving a prescription for pharmacotherapy ( p < .01 ) . At 3 months , there were no differences in quit attempts ( 58 % intervention , 64 % control ) , use of pharmacotherapy ( 34 % intervention , 46 % control ) , or abstinence ( 24 % intervention , 16 % control for self-reported abstinence ; 11 % intervention , 3.5 % control for cotinine-confirmed abstinence ) . The intervention group proved more cost-effective at achieving confirmed quits ( $ 6,800 vs. $ 9,700 ) . CONCLUSIONS We found few differences in outcomes between physicians exposed to a brief intervention and physicians who were intensively trained . Future studies should examine how tobacco dependence treatment can be further exp and ed in Medicaid programs The frequency of asking and advising adult patients about tobacco use was measured after an intervention to adopt smoking as a vital sign at 7 community health centers . The intervention consisted of training staff , revising forms and vital sign stamps , and disseminating educational material s. Documentation in medical charts was review ed for 1571 r and omly sample d patients in 2002 and 2003 . The point prevalence ( last encounter ) and period prevalence ( any annual encounter ) of asking patients about smoking increased significantly from 2002 to 2003 ( 59 % to 85 % , and 71 % to 97 % , respectively ) overall and at each health center . On advising smokers to quit , 4 health centers improved , but the overall point prevalence , 26 % , and period prevalence , 46 % , were unchanged over time . An intervention using multiple strategies may have contributed to improving the rates of asking but did not have as large or consistent an impact on rates of advising smokers to quit CONTEXT Most smokers with mental illness do not receive tobacco cessation treatment . OBJECTIVE To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder ( PTSD ) improves long-term smoking abstinence rates . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009 . INTERVENTION Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians ( integrated care [ IC ] ) vs referral to Veterans Affairs smoking cessation clinics ( SCC ) . Patients received smoking cessation treatment within 3 months of study enrollment . MAIN OUTCOME MEASURES Smoking outcomes included 12-month bioverified prolonged abstinence ( primary outcome ) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals . Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome . Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Question naire 9 , respectively , to determine if IC participation or quitting smoking worsened psychiatric status . RESULTS Integrated care was better than SCC on prolonged abstinence ( 8.9 % vs 4.5 % ; adjusted odds ratio , 2.26 ; 95 % confidence interval [ CI ] , 1.30 - 3.91 ; P = .004 ) . Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence ( 78/472 [ 16.5 % ] vs 34/471 [ 7.2 % ] , P < .001 ) and remained significant at 18 months ( 86/472 [ 18.2 % ] vs 51/471 [ 10.8 % ] , P < .001 ) . Number of counseling sessions received and days of cessation medication used explained 39.1 % of the treatment effect . Between baseline and 18 months , psychiatric status did not differ between treatment conditions . Posttraumatic stress disorder symptoms for quitters and nonquitters improved . Nonquitters worsened slightly on the Patient Health Question naire 9 relative to quitters ( differences ranged between 0.4 and 2.1 , P = .03 ) , whose scores did not change over time . CONCLUSION Among smokers with military-related PTSD , integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment result ed in greater prolonged abstinence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118534 AIM To evaluate the effectiveness in primary care of a stepped smoking cessation intervention based on the transtheoretical model of change . DESIGN Cluster r and omized trial ; unit of r and omization : basic care unit ( family physician and nurse who care for the same group of patients ) ; and intention-to-treat analysis . SETTING All interested basic care units ( n = 176 ) that worked in 82 primary care centres belonging to the Spanish Preventive Services and Health Promotion Research Network in 13 regions of Spain . PARTICIPANTS A total of 2,827 smokers ( aged 14 - 85 years ) who consulted a primary care centre for any reason , provided written informed consent and had valid interviews . MEASUREMENTS The outcome variable was the 1-year continuous abstinence rate at the 2-year follow-up . The main variable was the study group ( intervention/control ) . Intervention involved 6-month implementation of recommendations from a Clinical Practice Guideline which included brief motivational interviews for smokers at the precontemplation-contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help and reinforcing intervention in the maintenance stage . Control group involved usual care . Among others , characteristics of tobacco use and motivation to quit variables were also collected . FINDINGS The 1-year continuous abstinence rate at the 2-year follow-up was 8.1 % in the intervention group and 5.8 % in the control group ( P = 0.014 ) . In the multivariate logistic regression , the odds of quitting of the intervention versus control group was 1.50 ( 95 % confidence interval = 1.05 - 2.14 ) . CONCLUSIONS A stepped smoking cessation intervention based on the transtheoretical model significantly increased smoking abstinence at a 2-year follow-up among smokers visiting primary care centres OBJECTIVE To evaluate the impact of a locally adapted evidence -based quality improvement ( EBQI ) approach to implementation of smoking cessation guidelines into routine practice . DATA SOURCES / STUDY SETTING We used patient question naires , practice surveys , and administrative data in Veterans Health Administration ( VA ) primary care practice s across five southwestern states . STUDY DESIGN In a group-r and omized trial of 18 VA facilities , matched on size and academic affiliation , we evaluated intervention practice s ' abilities to implement evidence -based smoking cessation care following structured evidence review , local priority setting , quality improvement plan development , practice facilitation , expert feedback , and monitoring . Control practice s received mailed guidelines and VA audit-feedback reports as usual care . DATA COLLECTION To represent the population of primary care-based smokers , we r and omly sample d and screened 36,445 patients to identify and enroll eligible smokers at baseline ( n=1,941 ) and follow-up at 12 months ( n=1,080 ) . We used computer-assisted telephone interviewing to collect smoking behavior , nicotine dependence , readiness to change , health status , and patient sociodemographics . We used practice surveys to measure structure and process changes , and administrative data to assess population utilization patterns . PRINCIPAL FINDINGS Intervention practice s adopted multifaceted EBQI plans , but had difficulty implementing them , ultimately focusing on smoking cessation clinic referral strategies . While attendance rates increased ( p<.0001 ) , we found no intervention effect on smoking cessation . CONCLUSIONS EBQI stimulated practice s to increase smoking cessation clinic referrals and try other less evidence -based interventions that did not translate into improved quit rates at a population level CONTEXT Effective clinic-based , smoking-cessation activities are not widely implemented . OBJECTIVE To compare and contrast the smoking-cessation attitudes and clinical practice s of five types of primary healthcare team members . DESIGN AND SETTING From July to October 2002 , a cross-sectional survey was mailed to r and omly selected primary care physicians ( MDs ) , advanced practice nurses ( APRNs ) , registered nurses ( RNs ) , licensed practical nurses ( LPNs ) , and medical assistants ( MAs ) . MAIN OUTCOME MEASURES Factors associated with limited smoking-cessation service delivery . RESULTS The overall response rate was 68 % ( n = 3021 ) . Most respondents reported that patients ' smoking status was consistently documented at their clinic ( 79 % ) ; other system prompts were less common ( 30 % ) . Many respondents reported documenting smoking status or recommending quitting ; few reported consistently assessing , assisting , or arranging follow-up . The mean rank of smoking cessation as an important preventive service among nine preventive services declined from MDs ( 1.9 ) to APRNs ( 2.5 ) , RNs ( 3.4 ) , LPNs ( 4.2 ) , and MAs ( 4.6 ) . Smoking prevalence increased from 1 % in MDs to 3 % APRNs , 9 % RNs , 17 % LPNs , and 22 % MAs . Those who reported no consistent smoking-cessation service delivery were more likely to be RNs , LPNs , or MAs , currently smoke , and work more hours . They were less likely to consider patients receptive to cessation messages , to consider themselves qualified to counsel on smoking , or to work in clinics that had smoking-cessation guidelines or system prompts such as chart reminders . CONCLUSIONS Smoking-cessation service delivery may be enhanced if educational offerings , system changes , and training include all clinical staff members IMPORTANCE Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence -based treatments , such as quitline ( telephone-based tobacco cessation services ) assistance . The most notable examples are the 5 As ( Ask , Advise , Assess , Assist , Arrange ) and Ask . Advise . Refer . ( AAR ) programs . Unfortunately , rates of primary care referrals to quitlines are low , and most referred smokers fail to call for assistance . OBJECTIVE To evaluate a new approach -- Ask-Advise-Connect (AAC)-- design ed to address barriers to linking smokers with treatment . DESIGN A pair-matched , 2-treatment-arm , group-r and omized design in 10 family practice clinics in a single metropolitan area . Five clinics were r and omized to the AAC ( intervention ) and 5 to the AAR ( control ) conditions . In both conditions , clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record , and smokers were given brief advice to quit . In the AAC clinics , the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily , and patients were called proactively by the quitline within 48 hours . In the AAR clinics , smokers were offered a quitline referral card and encouraged to call on their own . All data were collected from February 8 through December 27 , 2011 . SETTING Ten clinics in Houston , Texas . PARTICIPANTS Smoking status assessment s were completed for 42,277 patients ; 2052 unique smokers were identified at AAC clinics , and 1611 smokers were identified at AAR clinics . INTERVENTIONS Linking smokers with quitline-delivered treatment . MAIN OUTCOME MEASURE Impact was based on the RE- AIM ( Reach , Efficacy , Adoption , Implementation , and Maintenance ) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment . RESULTS In the AAC clinics , 7.8 % of all identified smokers enrolled in treatment vs 0.6 % in the AAR clinics ( t4 = 9.19 [ P < .001 ] ; odds ratio , 11.60 [ 95 % CI , 5.53 - 24.32 ] ) , a 13-fold increase in the proportion of smokers enrolling in treatment . CONCLUSIONS AND RELEVANCE The system changes implemented in the AAC approach could be adopted broadly by other health care systems and have tremendous potential to reduce tobacco-related morbidity and mortality The prevalence of adult tobacco users who utilize the emergency department as patients or parents is disproportionately higher than the national average rates of tobacco use . Thus , it is advised that the emergency department be utilized as a venue for providing tobacco cessation counseling to adult tobacco users . Using a r and omized control trial design , this pilot study evaluated the effect of a brief tobacco cessation intervention for tobacco using parents of children brought to a pediatric emergency department . Participants received either usual care or a brief tobacco cessation intervention based on the first 2 of the 5A 's of the Clinical Practice Guidelines and fax referral to the Quitline . The primary outcome was self-reported repeated point prevalence of tobacco use at 6 weeks and 3 months following the intervention . Secondary aims included number of quit attempts , increases in readiness to quit , comparisons of participants who were successfully retained , and contact rates by Quitline counselors . At 3-month follow-up , compared to the Usual Care Control group , intervention participants were more likely to have made at least one quit attempt ( 59 % vs. 34 % ; p<.01 ) , be seriously thinking about quitting ( 68 % vs. 37 % ; p<.001 ) , and have higher Ladder scores ( 6.2 vs. 5.3 ; p<.05 ) . Study personnel were able to contact 68 % and 52 % , respectively , of participants at 6-week and 3-month follow-up . Quitline counselors were unable to reach 54 % of participants . Our results reveal increased intentions to quit and trends toward quitting , however we experienced difficulties with participant retention . Suggestions for improvements in point prevalence and retention are given Objective : To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics . Design : Group r and omised trial . Setting : 22 antenatal clinics in New South Wales , Australia . Intervention : Clinics were allocated to a simple dissemination ( SD ) condition ( 11 clinics ) which received a mail-out of programme re sources or to an intensive dissemination ( ID ) condition ( 11 clinics ) which included the mail-out plus feedback , training , and ongoing support with midwife facilitator . Main outcome measures : Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination . Outcomes were : ( 1 ) levels of smoking status assessment by clinic staff ; ( 2 ) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice ; ( 3 ) proportion of these women who had quit ( self report and expired air carbon monoxide ( CO ) ) ; and ( 4 ) smoking prevalence among all women ( self report and CO ) . Subjects : 5849 women pre-dissemination ( 2374 SD , 3475 ID ) and weighted sample of 5145 women post-dissemination ( 2302 SD , 2843 ID ) . Results : There were no significant differences between the groups on change on any outcome . Change in either group was minimal . In the post-dissemination survey , the cessation proportions were 6.4 % ( SD ) and 10.5 % ( ID ) . Conclusions : Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term . Alternative strategies should be implemented and evaluated . The findings reinforce the importance of a whole population approach to tobacco control STUDY OBJECTIVE To examine community pharmacy practice with regard to providing smoking-cessation counseling . DESIGN Mailed survey . SETTING Iowa community pharmacies . PARTICIPANTS A stratified r and om sample of pharmacists statewide . MEASUREMENTS AND MAIN RESULTS Descriptive statistics were computed for all study variables . Fisher exact test or chi2 analysis was performed on selected variables to determine the relationship of each item with pharmacists routinely offering smokers suggestions for quitting . Responses from 129 ( 38.2 % ) of 338 pharmacists indicated that although most felt it is important to offer smoking-cessation counseling , about half actually offer this service . Most pharmacists indicated they are prepared to provide counseling , but fewer than 25 % had received formal training or were aware of national clinical practice guidelines . Those who had received specific training ( p=0.020 ) or recently attended an educational program ( p=0.014 ) on smoking cessation were more likely to counsel smokers . Primary barriers to providing counseling were lack of time , inability to identify smokers , low patient dem and , and lack of reimbursement . CONCLUSION Our findings suggest that opportunities exist for improving pharmacist education and reducing practice barriers in order to bridge the gap between pharmacists ' knowledge and attitudes related to smoking-cessation counseling and their provision of patient counseling in community pharmacy practice OBJECTIVES We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation , reduction in tobacco use , number of quit attempts , and change in readiness to quit . METHODS We r and omized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states ( Mississippi , New York , and Oregon ) to the intervention ( brief advice and assistance , including nicotine replacement therapy ) or usual care group . RESULTS We enrolled 2549 smokers . Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up , for both point prevalence ( F(1,12 ) = 6.84 ; P < .05 ) and prolonged abstinence ( F(1,12 ) = 14.62 ; P < .01 ) than did those in the usual care group . CONCLUSIONS The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers . Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans This study was undertaken to evaluate a tailored smoking cessation intervention , which is applicable to Korean culture , using the Agency for Health Care Policy and Research ( AHCPR ) guideline . On-site counselors provided brief nurse-assisted smoking cessation counseling , including follow-up telephone support , to prevent a relapse in 200 r and omly assigned smoking patients . These patients were referred by their physicians regardless of their willingness in smoking cessation in the outpatient department at a university hospital . Nicotine replacement therapy was not provided . Another 201 patients served as a control . After 5 months , current smoking cessation was self-reported on the phone and vali date d later by a portable carbon monoxide analyzer . After 5 months , the participants in the intervention group were no more likely to quit smoking than the control group . A subgroup analysis by age showed that the intervention among 166 younger smokers ( aged 49 or less ) was significantly more likely to be effective { risk ratio = 5.76 [ 95 % confidence interval ( CI ) 1.34 - 24.74 ] } than it was among 235 older smokers ( aged 50 or more ) [ risk ratio = 1.03 ( 95 % CI 0.53 - 1.99 ) ] . This study suggests a smoking cessation intervention using the AHCPR guideline tailored for Koreans , is effective for assisting out patients aged 49 or younger to quit smoking 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 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 OBJECTIVES A r and omized trial evaluated the impact of smoking cessation interventions on point prevalence and consecutive quit rates at an Australian public prenatal clinic . METHODS Self-reports and urine cotinine tests confirmed patients ' smoking status at the midpoint and end of pregnancy and 6 weeks postpartum . RESULTS At all points , vali date d abstinence rates were significantly higher in the experimental group than in the control group . The rate of failed biochemical validation was significantly higher in the control group than in the experimental group . CONCLUSIONS Prenatal clinic staff can significantly increase quit rates by using cognitive-behavioral strategies . Brief advice appears to be ineffective BACKGROUND Decreases in smoking prevalence from recent decades have slowed , and national goals to reduce tobacco use remain unmet . Healthcare providers , including those in physician and dental teams , have access to evidence -based guidelines to help patients quit smoking . Translation of those guidelines into practice , however , remains low . Approaches that involve screening for drug use , brief intervention , and referral to treatment ( SBIRT ) are a promising , practical solution . PURPOSE This study examined whether dentists and dental hygienists would assess interest in quitting , deliver a brief tobacco intervention , and refer to a tobacco quitline more frequently as reported by patients if given computer-assisted guidance in an electronic patient record versus a control group providing usual care . DESIGN A blocked , group-r and omized trial was conducted from November 2010 to April 2011 . R and omization was conducted at the clinic level . Patients nested within clinics represented the lowest-level unit of observation . SETTING / PARTICIPANTS Participants were patients in HealthPartners dental clinics . INTERVENTION Intervention clinics were given a computer-assisted tool that suggested scripts for patient discussion s. Usual care clinics provided care without the tool . MAIN OUTCOME MEASURES Primary outcomes were post-appointment patient reports of the provider assessing interest in quitting , delivering a brief intervention , and referring them to a quitline . RESULTS Patient telephone surveys ( 72 % response rate ) indicated that providers assessed interest in quitting ( control 70 % vs intervention 87 % , p=0.0006 ) ; discussed specific strategies for quitting ( control 26 % vs intervention 47 % , p=0.003 ) ; and referred the patient to a tobacco quitline ( control 17 % vs intervention 37 % , p=0.007 ) more frequently with the support of a computer-assisted tool integrated into the electronic health record . CONCLUSIONS Clinical decision support embedded in electronic health records can effectively help providers deliver tobacco interventions . These results build on evidence in medical setting s supporting this approach to improve provider-delivered tobacco cessation . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT01584882 BACKGROUND Previous studies have attempted to investigate the impact of smoking cessation on lung cancer survival but have been limited by small numbers of former smokers and incomplete data . METHODS Over a six-year period , 5229 patients with non-small-cell lung cancer ( NSCLC ) and small-cell lung cancer ( SCLC ) were enrolled in a prospect i ve cohort of whom 2052 were former smokers . Patient 's characteristics were obtained from medical records and a baseline interview . Vital status was determined through multiple sources . Cox proportional hazards models were used to estimate the effect of smoking abstinence on post-diagnosis mortality . RESULTS For all patients with NSCLC , the median survival among never , former , and current smokers was 1.4 years , 1.3 years , and 1.1 years , respectively ( P < 0.01 ) . Female NSCLC patients had a significantly lower risk of mortality with a longer duration of smoking abstinence ( RR per 10 years of smoking abstinence = 0.85 ; 95 % CI : 0.75 , 0.97 ) . No effect of smoking abstinence on mortality was observed for women with SCLC or for men with either histologic group . CONCLUSIONS The identification of smoking history as a prognostic factor in lung cancer survival supports previous research suggesting a direct biologic effect of smoking on survival . However , this effect may vary by sex and type of lung cancer The electronic health record ( EHR ) may be an effective tool to help clinicians address tobacco use more consistently . To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline , we conducted a cluster r and omized clinical trial ( feedback versus no feedback ) within 19 primary care clinics in Oregon . Intervention clinics received provider-specific monthly feedback reports generated from EHR data . The reports rated provider performance in asking , advising , assessing , and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care . During 12 months of follow-up , EHR-documented rates of advising , assessing , and assisting were significantly improved in the intervention clinics compared with the control clinics ( p<.001 ) . A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline . EHR-generated provider feedback improved documentation of assistance with tobacco cessation . Connecting physician offices to a state-level quitline was feasible and well accepted OBJECTIVES To evaluate the effect of a provider counseling and office systems intervention in obstetric , pediatric , and Special Supplemental Nutrition Program for Women , Infants and Children ( WIC ) clinics on smoking and relapse rates in pregnant and postpartum women . METHODS Five community health centers were r and omized to special intervention ( SI ) or usual care ( UC ) . Subjects ( n = 601 ) were current smokers or had quit with pregnancy . Prenatal and postpartum interviews assessed smoking status and related factors . Data were collected between May 1997 and November 2000 . RESULTS There was a statistically significant difference in 30-day abstinence rates between SI ( 26 % ) and UC ( 12 % ) conditions at the end of pregnancy among women who had not quit spontaneously with pregnancy ( odds ratio [OR]=2.57 , p = 0.05 ) . This effect remained at 1 month postpartum but was lost at 3- and 6-month postpartum follow-ups . CONCLUSIONS Brief interventions delivered by healthcare providers during routine prenatal care increased smoking abstinence during pregnancy among women who did not quit spontaneously . Interventions extended into postpartum care did not affect relapse and smoking rates postdelivery |
427 | 26,409,842 | None of the nonrevascularization-based treatments were associated with a significant effect on mortality .
Very low- quality evidence , mainly due to imprecision and increased risk of bias , suggests that intermittent pneumatic compression and spinal cord stimulators may reduce the risk of amputations . | OBJECTIVE The aim of this systematic review was to synthesize the existing evidence about various nonrevascularization-based therapies used to treat patients with severe or critical limb ischemia ( CLI ) who are not c and i date s for surgical revascularization . | Background —Bone-marrow mononuclear cell ( BM-MNC ) implantation improves ischemic symptoms in patients with critical limb ischemia ( CLI ) . The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI . Methods and Results —We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI , including 25 patients with peripheral arterial disease ( PAD ) and 26 patients with Buerger disease . Forty-six CLI patients who had no BM-MNC implantation served as control subjects . Median follow-up period was 4.8 years . The 4-year amputation-free rates after BM-MNC implantation were 48 % in PAD patients and 95 % in Buerger disease , and they were 0 % in control PAD patients and 6 % in control Buerger disease . The 4-year overall survival rates after BM-MNC implantation were 76 % in PAD patients and 100 % in Buerger disease , and they were 67 % in control PAD patients and 100 % in control Buerger disease . Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation . In Buerger disease , ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up . However , in patients with PAD , ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels . Conclusions —These findings suggest that BM-MNC implantation is safe and effective in patients with CLI , especially in patients with Buerger disease . Clinical Trial Registration —URL : http://home.hiroshima-u.ac.jp/angio/. Unique identifier : 001769 UNLABELLED The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expressing vascular endothelial and hepatocyte growth factors in patients with critical limb ischemia . The study included 43 patients : 29 in the treatment group and 14 allocated to the placebo group . The primary end points were the rate of major amputations and the clinical safety of the method . Secondary end points were improvement of pain at rest , walking ability and the ankle/brachial pressure index . The overall major amputation rate was 31.04 % in the treatment group and 71.42 % in the placebo group ( p = 0.029 ) . Pain at rest was improved in 65 % of patients in the gene therapy group and in 7 % in the placebo group ( p = 0.0006 ) . There were no significant adverse effects in the treatment group . CONCLUSION Gene therapy with vascular endothelial and hepatocyte growth factors is therapeutically safe and reduces the rate of major amputations and relieves pain at rest in patients with critical limb ischemia OBJECTIVES We have previously reported the results of a dose-finding phase II trial showing that HGF angiogenic gene therapy can increase TcPO2 compared with placebo in patients with critical limb ischemia ( CLI ) . The purpose of this r and omized placebo controlled multi-center trial was to further assess the safety and clinical efficacy of a modified HGF gene delivery technique in patients with CLI and no revascularization options . METHODS Patients with lower extremity ischemic tissue loss ( Rutherford 5 and 6 ) received three sets of eight intramuscular injections every 2 weeks of HGF plasmid under duplex ultrasound guidance . Injection locations were individualized for each patient based on arteriographically defined vascular anatomy . Primary safety end point was incidence of adverse events ( AE ) or serious adverse events ( SAE ) . Clinical end points included change from baseline in toe brachial index ( TBI ) , rest pain assessment by a 10 cm visual analogue scale ( VAS ) as well as wound healing , amputation , and survival at 3 and 6 months . RESULTS R and omization ratio was 3:1 HGF ( n = 21 ) vs placebo ( n = 6 ) . Mean age was 76 ± 2 years , with 56 % male and 59 % diabetic . There was no difference in demographics between groups . There was no difference in AEs or SAEs , which consisted mostly of transient injection site discomfort , worsening of CLI , and intercurrent illnesses . Change in TBI significantly improved from baseline at 6 months in the HGF-treated group compared with placebo ( 0.05 ± 0.05 vs -0.17 ± 0.04 ; P = .047 ) . Change in VAS from baseline at 6 months was also significantly improved in the HGF-treated group compared with placebo ( -1.9 ± 1.3 vs + 0.06 ± 0.2 ; P = .04 ) . Complete ulcer healing at 12 months occurred in 31 % of the HGF group and 0 % of the placebo ( P = .28 ) There was no difference in major amputation of the treated limb ( HGF 29 % vs placebo 33 % ) or mortality at 12 months ( HGF 19 % vs placebo 17 % ) between groups . CONCLUSION HGF gene therapy using a patient vascular anatomy specific delivery technique appears safe , maintained limb perfusion , and decreased rest pain in patients with CLI compared with placebo . A larger study to assess the efficacy of this therapy on more clinical ly relevant end points is warranted Background — The Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia ( HGF-STAT trial ) determined the effect of hepatocyte growth factor ( HGF ) plasmid on safety and limb tissue perfusion as measured by transcutaneous oxygen tension ( TcPo2 ) in patients with critical limb ischemia ( CLI ) . Methods and Results — R and omized patients with rest pain or ischemic ulcers and TcPo2 < 40 mm Hg and /or toe pressure < 50 mm Hg received placebo or HGF-plasmid intramuscular injection as follows : 0.4 mg at days 0 , 14 , and 28 ( low dose ) ; 4.0 mg at days 0 and 28 ( middle dose ) ; or 4.0 mg at days 0 , 14 , and 28 ( high dose ) . Patients were evaluated for safety , changes in TcPo2 and ankle and toe pressure , amputation , and wound healing . Ninety-three of 104 treated patients were evaluated for safety ( mean age 70 years , 63 % male , 53 % diabetic , 64 % with tissue loss , mean ankle-brachial index 0.41 , and mean toe pressure 26 mm Hg ) . Adverse events occurred in 86 % of the patients , most of which were related to CLI or comorbid conditions and were not different between groups . TcPo2 ( mean±SE ) increased at 6 months in the high-dose group ( 24.0±4.2 mm Hg , 95 % CI 15.5 to 32.4 mm Hg ) compared with the placebo ( 9.4±4.2 mm Hg , 95 % CI 0.9 to 17.8 ) , low-dose ( 11.1±3.7 mm Hg , CI 3.7 to 18.7 mm Hg ) , and middle-dose ( 7.3±4.8 mm Hg , CI −2.2 to 17.0 mm Hg ) groups ( ANCOVA P=0.0015 ) . There was no difference between groups in secondary end points , including ankle-brachial index , toe-brachial index , pain relief , wound healing , or major amputation . Conclusions — Intramuscular injection of HGF plasmid was safe and well tolerated . Larger studies to determine whether HGF plasmid can improve wound healing and limb salvage in patients with CLI are warranted BACKGROUND Patients with intermittent claudication ( IC ) could benefit from low-cost , effective rehabilitative programs . This retrospective study evaluates compliance , impact on Quality of Life ( QoL ) and cost-effectiveness of a hospital prescribed , at-home performed ( Test-in/Train-out ) rehabilitative program for patients with IC . METHODS AND RESULTS Two-hundred and eighty-nine patients with IC ( 71 ± 10.1 years , M = 210 ) were enrolled for a 2-year period . Two daily 10-min home walking sessions at maximal asymptomatic speed were prescribed , with serial check-ups at the hospital . Compliance with the program was assessed by assigning a score of 1 ( lowest compliance ) to 4 ( highest compliance ) . The SF-36 question naire and a constant-load treadmill test were used to evaluate QoL and Initial/Absolute Claudication Distance , respectively . Both direct and indirect costs of the program were considered for cost-effectiveness analysis . Two-hundred and fifty patients ( 70.5 ± 9.2 years , M = 191 ) , at Fontaine 's II-B stage ( 86 % ) , were included in the study . No adverse events were reported . The average compliance score was 3.1 . At discharge , both SF-36 domains and walking performance significantly increased ( P < 0.0001 ) . A total of 1,839 in-hospital check-ups ( 7.36 /patient ) were performed . Direct and indirect costs represented 93 % and 7 % of the total costs , respectively . The average costs of a visit and of a therapy cycle were C68.93 and C507.20 , respectively . The cost to walk an additional meter before stopping was C9.22 . CONCLUSIONS A Test-in/Train-out program provided favourable patient compliance , QoL impact and cost-effectiveness in patients with IC Ixmyelocel-T is a patient-specific , exp and ed , multicellular therapy evaluated in patients with lower extremity critical limb ischemia ( CLI ) with no options for revascularization . This r and omized , double-blind , placebo-controlled , phase 2 trial ( RESTORE-CLI ) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo . Patients received one-time injections over 20 locations in a single leg and were followed for 12 months . Safety assessment s included occurrence of adverse events . Efficacy assessment s included time to first occurrence of treatment failure ( TTF ; major amputation of injected leg ; all-cause mortality ; doubling of total wound surface area from baseline ; de novo gangrene ) and amputation-free survival ( AFS ; major amputation of injected leg ; all-cause mortality ) . A total of 77 patients underwent bone marrow or sham aspiration ; 72 patients received ixmyelocel-T ( 48 patients ) or placebo ( 24 patients ) . Adverse event rates were similar . Ixmyelocel-T treatment led to a significantly prolonged TTF ( P = 0.0032 , logrank test ) . AFS had a clinical ly meaningful 32 % reduction in event rate that was not statistically significant ( P = 0.3880 , logrank test ) . Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced ( TTF : P < 0.0001 , AFS : P = 0.0802 , logrank test ) . Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option BACKGROUND Patients with critical limb ischaemia have a high rate of amputation and mortality . We tested the hypothesis that non-viral 1 fibroblast growth factor ( NV1FGF ) would improve amputation-free survival . METHODS In this phase 3 trial ( EFC6145/TAMARIS ) , 525 patients with critical limb ischaemia unsuitable for revascularisation were enrolled from 171 sites in 30 countries . All had ischaemic ulcer in legs or minor skin gangrene and met haemodynamic criteria ( ankle pressure < 70 mm Hg or a toe pressure < 50 mm Hg , or both , or a transcutaneous oxygen pressure < 30 mm Hg on the treated leg ) . Patients were r and omly assigned to either NV1FGF at 0·2 mg/mL or matching placebo ( visually identical ) in a 1:1 ratio . R and omisation was done with a central interactive voice response system by block size 4 and was stratified by diabetes status and country . Investigators , patients , and study teams were masked to treatment . Patients received eight intramuscular injections of their assigned treatment in the index leg on days 1 , 15 , 29 , and 43 . The primary endpoint was time to major amputation or death at 1 year analysed by intention to treat with a log-rank test using a multivariate Cox proportional hazard model . This trial is registered with Clinical Trials.gov , number NCT00566657 . FINDINGS 259 patients were assigned to NV1FGF and 266 to placebo . All 525 patients were analysed . The mean age was 70 years ( range 50 - 92 ) , 365 ( 70 % ) were men , 280 ( 53 % ) had diabetes , and 248 ( 47 % ) had a history of coronary artery disease . The primary endpoint or components of the primary did not differ between treatment groups , with major amputation or death in 86 patients ( 33 % ) in the placebo group , and 96 ( 36 % ) in the active group ( hazard ratio 1·11 , 95 % CI 0·83 - 1·49 ; p=0·48 ) . No significant safety issues were recorded . INTERPRETATION TAMARIS provided no evidence that NV1FGF is effective in reduction of amputation or death in patients with critical limb ischaemia . Thus , this group of patients remains a major therapeutic challenge for the clinician . FUNDING Sanofi-Aventis , Paris , France PURPOSE Patients with non-reconstructable critical limb ischemia generally undergo medical treatment only to prevent or postpone amputation . There is some evidence that spinal cord stimulation ( SCS ) stimulates ischemic wound healing . Thus , this could benefit limb survival through improved skin perfusion . We investigated the effect of SCS versus conservative treatment on skin microcirculation in relation to treatment outcome in patients with non-reconstructable critical limb ischemia . METHODS St and ard medical treatment plus SCS was compared with only st and ard medical treatment in a multicenter r and omized controlled trial comprised of 120 patients with surgically non-reconstructable chronic rest pain or ulceration . We investigated skin microcirculation by means of capillary microscopy , laser Doppler perfusion , and transcutaneous oxygen measurements in the foot . The microcirculatory status just before treatment was classified in three categories ( poor , intermediate , and good ) and was related to limb survival after a minimum follow-up period of 18 months . RESULTS Clinical parameters , peripheral blood pressures , and limb survival rates showed no significant differences between the SCS and st and ard groups during the follow-up period . In both treatment groups , amputation frequency after 18 months was high in patients with an initially poor microcirculatory skin perfusion ( SCS 80 % vs st and ard treatment 71 % ; NS ) and low in those with a good skin perfusion ( 29 % vs 11 % , respectively ; NS ) . In patients with an intermediate skin microcirculation amputation , frequency was twice as low in patients additionally treated with SCS as in the st and ard treatment group ( 48 % vs 24 % ; P = .08 ) . In these patients , microcirculatory reactive hyperemia during the follow-up period reduced in the st and ard group but not in the SCS group ( P < .01 ) . CONCLUSION Selection on the basis of the initial microcirculatory skin perfusion identifies patients in whom SCS can improve local skin perfusion and limb survival OBJECTIVES This study was design ed to test the hypothesis that spinal cord stimulation ( SCS ) improves limb salvage in patients with inoperable severe leg ischaemia . DESIGN Prospect i ve r and omised controlled study with 18 months follow-up . SETTING Vascular surgical units in two university hospitals . MATERIAL S Atherosclerotic ( n = 41 ) and diabetic ( n = 10 ) patients having chronic leg ischaemia with rest pain and /or ischaemic ulcerations due to technically inoperable arterial occlusions . CHIEF OUTCOME MEASURES Limb salvage and amount of tissue loss within 18 months , pain relief . MAIN RESULTS Twenty-five patients were r and omized to SCS and 26 to analgesic ( control ) treatment . Macrocirculatory parameters were not different in the two groups during follow-up . Long-term pain relief was observed only in the SCS group . At 18 months , limb salvage rates in the SCS and control groups were 62 % and 45 % ( N.S. ) . Tissue loss was less ( p = 0.05 ) in the SCS group . A subgroup analysis of patients without arterial hypertension showed a significantly lower amputation rate in the SCS vs the control group . CONCLUSIONS SCS provided long-term pain relief but limb salvage at 18 months was not significantly improved by SCS in this rather small study . The results suggest that SCS may reduce amputation levels in patients with severe inoperable leg ischaemia and be most effective in patients without arterial hypertension Background Short-term ( within 6 weeks follow-up ) clinical studies indicate that implantation of bone marrow cells ( BMC s ) into ischemic limbs may improve peripheral ischemia . Here , the long-term safety and feasibility of intraarterial autologous BMC s with oral treatment with antioxidants and L-arginine were investigated in patients with critical ischemia on account of advanced atherosclerotic peripheral arterial disease ( PAD ) . Methods Eighteen patients with PAD ( advanced III/IV Fontaine stages ) were enrolled in this study ( NCT00306085 ) . An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control . The BMC -treated group received two doses of BMC s in the leg arteries ( time 0 and 45 days ) . After 30 days from the first BMC dose , patients received daily antioxidants , and l-arginine . Therapeutic neoangiogenesis was estimated by angiography and laser Doppler capillaroscopy . Results Ankle brachial index improvement ( ΔABI : > 0.1 ) was seen in 10 patients at 3 months and in 12 patients at 12–18 months . Ischemic ulcers improved in 13 patients ( after 6–12 months ) . Although two patients underwent amputation , the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months . Among conservative patients , 10 underwent amputation in comparison with two BMC -treated patients ( 55.6 vs. 13.3 % ; P = 0.014 ) . Conclusion This small study shows that intraarterial autologous BMC and antioxidants and l-arginine therapy is safe and effective in patients with advanced atherosclerotic PAD with positive effects until 18 months . Eur J Cardiovasc Prev Rehabil 15:709–718 © 2008 The European Society of This study was done to evaluate the effect of spinal cord stimulation ( SCS ) on critical limb ischemia and to report technical problems and complications . One hundred and twenty patients with critical limb ischemia were eligible for r and omization between medical treatment and medical treatment plus SCS . Sixty received a spinal cord stimulator ( Itrel II ; Medtronic , Minneapolis , Minn. , USA ) . Primary outcome measures were limb salvage and pain relief . The mean pain reduction in both treatment groups was 50 % ( from 5 to 2.5 on the visual analog scale ) . The 2-year limb survival was 52 % ( SCS ) versus 46 % ( st and ard treatment ; p = 0.47 ) . The number of patients undergoing major amputations in the SCS group with intermediate TcpO2 values was half of that in the st and ard group ( 14 vs. 28 ; 24 vs. 48 % ; p = 0.17 ) . Implantation was successful in 51 patients . Technical problems such as loss of stimulation due to lead displacement occurred in 13 patients ( 22 % ) , local infection at the site of implantation occurred in 3 patients ( 5 % ) , result ing in a total complication rate of 27 % . Prematue depletion of the battery occurred within 2 years in 3 patients ( 5 % ) . There were no lead fractures , epidural infections , hematoma or cerebrospinal fluid leakage . Training of physicians and better reliability of the hardware should reduce the frequency of technical problems . Lead displacement remains the major technical problem . The search for prognostic factors of limb salvage is important . One microcirculatory measurement ( TcpO2 ) seems to have a prognostic value , which remains to be described more precisely PURPOSE Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia ( CLI ) secondary to atherosclerotic peripheral arterial disease . The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies . Lipo-ecraprost is a lipid-encapsulated prostagl and in E1 prodrug with the potential to deliver active prostagl and in to the site of critical arterial ischemia . The current trial was design ed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options . METHODS The study was r and omized , multicenter , double blind , and placebo controlled . Patients who met clinical and hemodynamic criteria were r and omized to receive placebo or lipo-ecraprost ( 60 microg ) administered intravenously on each of 5 days per week , for a total of 8 weeks . The study 's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days ( 6 months ) . RESULTS The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol -specified interim analysis for futility . At the time of termination , 383 of the planned 560 patients had been r and omized , of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population . Twenty-three patients were lost to follow-up and were not available for 6-month assessment s. At 6 months of follow-up , there were 23 amputations in the 177 patients who received placebo , and 29 amputations in the 179 patients r and omized to lipo-ecraprost . At 6 months , 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm . Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms . CONCLUSION Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not c and i date s for revascularization OBJECTIVE To determine the effect of spinal cord stimulation ( SCS ) on limb survival in patients with non-reconstructable critical leg ischaemia , and the value of patient selection on the basis of transcutaneous oxygen pressure ( TcpO2 ) measurements and trial screening . DESIGN A prospect i ve , controlled , European multicentre study . METHODS Non-reconstructable patients with stable critical leg ischaemia were divided into three groups . The SCS-Match group comprised patients with a baseline forefoot TcpO2 of < 30 mmHg and both sufficient pain relief and sufficient paraesthesia coverage ( > 75 % ) after a test stimulation period of at least 72 h. If baseline TcpO2 was < 10 mmHg , the TcpO2 should have exceeded 20 mmHg after test stimulation . The SCS-Match group was compared with patients not meeting these criteria , who were treated either with SCS ( SCS-No-Match ) or without SCS ( No-SCS ) . RESULTS At baseline , the mean ( + /- SD ) supine TcpO2 was 14.9 + /- 8.3 mmHg in the SCS-Match group ( n = 41 ) , 11.3 + /- 13.3 mmHg in the SCS-No-Match group ( n = 32 ) and 15.3 + /- 17.1 mmHg in the No-SCS group ( n = 39 ) . In the SCS-Match group a significant improvement in pain relief ( p < 0.005 ) and TcpO2 ( p < 0.001 ) was seen . After 12 months , cumulative limb survival of patients treated with SCS was significantly better than that of patients not treated with SCS ( p < 0.03 ) , and limb survival in the SCS-Match group was significantly higher ( p < 0.03 ) than that in the SCS-No-Match and No-SCS groups ( 78 , 55 and 45 % , respectively ) . CONCLUSION SCS treatment of non-reconstructable critical leg ischaemia provides a significantly better limb survival rate compared with conservative treatment . Patient selection based on TcpO2 and the results of trial screening further increase the probability of limb survival after SCS therapy This study evaluated the efficacy and safety of intramuscular administration of NV1FGF , a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 ( FGF-1 ) , versus placebo , in patients with critical limb ischemia ( CLI ) . In a double-blind , r and omized , placebo-controlled , European , multinational study , 125 patients in whom revascularization was not considered to be a suitable option , presenting with nonhealing ulcer(s ) , were r and omized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1 , 15 , 30 , and 45 ( total 16 mg : 4 × 4 mg ) . The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25 . Secondary end points included ankle brachial index ( ABI ) , amputation , and death . There were 107 patients eligible for evaluation . Improvements in ulcer healing were similar for use of NV1FGF ( 19.6 % ) and placebo ( 14.3 % ; P = 0.514 ) . However , the use of NV1FGF significantly reduced ( by twofold ) the risk of all amputations [ hazard ratio ( HR ) 0.498 ; P = 0.015 ] and major amputations ( HR 0.371 ; P = 0.015 ) . Furthermore , there was a trend for reduced risk of death with the use of NV1FGF ( HR 0.460 ; P = 0.105 ) . The adverse event incidence was high , and similar between the groups . In patients with CLI , plasmid-based NV1FGF gene transfer was well tolerated , and result ed in a significantly reduced risk of major amputation when compared with placebo |
428 | 28,322,634 | Few studies demonstrated significant improvements in the primary outcomes .
In conclusion , there is limited evidence on the effectiveness of end-of-life decision support for critically ill patients and their surrogate decision makers . | Determining effective decision support strategies that enhance quality of end-of-life decision making in the intensive care unit is a research priority .
This systematic review identified interventional studies describing the effectiveness of decision support interventions administered to critically ill patients or their surrogate decision makers . | BACKGROUND Formal family meetings have been recommended as a useful approach to assist in goal setting , facilitate decision making , and reduce use of ineffective re sources in the ICU . We examined patient outcomes before and after implementation of an intensive communication system ( ICS ) to test the effect of regular , structured formal family meetings on patient outcomes among long-stay ICU patients . METHODS One hundred thirty-five patients receiving usual care and communication were enrolled as the control group , followed by enrollment of intervention patients ( n = 346 ) , from five ICUs . The ICS included a family meeting within 5 days of ICU admission and weekly thereafter . Each meeting discussed medical up date , values and preferences , and goals of care ; treatment plan ; and milestones for judging effectiveness of treatment . RESULTS Using multivariate analysis , there were no significant differences between control and intervention patients in length of stay ( LOS ) , the primary end point . Similarly , there were no significant differences in indicators of aggressiveness of care or treatment limitation decisions ( ICU mortality , LOS , duration of ventilation , treatment limitation orders , or use of tracheostomy or percutaneous gastrostomy ) . Exploratory analysis suggested that in the medical ICUs , the intervention was associated with a lower prevalence of tracheostomy among patients who died or had do-not-attempt-resuscitation orders in place . CONCLUSIONS The negative findings of the main analysis , in combination with preliminary evidence of differences among types of unit , suggest that further examination of the influence of patient , family , and unit characteristics on the effects of a system of regular family meetings may be warranted . Despite the lack of influence on patient outcomes , structured family meetings may be an effective approach to meeting information and support needs . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01057238 ; URL : www . clinical trials.gov BACKGROUND Ten percent to 20 % of trauma patients admitted to the intensive care unit ( ICU ) will die from their injuries . Providing appropriate end-of-life care in this setting is difficult and often late in the patients ' course . Patients are young , prognosis uncertain , and conflict common around goals of care . We hypothesized that early , structured communication in the trauma ICU would improve end-of-life care practice . METHODS Prospect i ve , observational , prepost study on consecutive trauma patients admitted to the ICU before and after a structured palliative care intervention was integrated into st and ard ICU care . The program included part I , early ( at admission ) family bereavement support , assessment of prognosis , and patient preferences , and part II ( within 72 hours ) interdisciplinary family meeting . Data on goals of care discussion s , do-not-resuscitate ( DNR ) orders and withdrawal of life support ( W/D ) were collected from physician rounds , family meetings , and medical records . RESULTS Eighty-three percent of patients received part I and 69 % part II intervention . Discussion of goals of care by physicians on rounds increased from 4 % to 36 % of patient-days . During intervention , rates of mortality ( 14 % ) , DNR ( 43 % ) , and W/D ( 24 % ) were unchanged , but DNR orders and W/D were instituted earlier in hospital course . ICU length of stay was decreased in patients who died . CONCLUSIONS Structured communication between physician and families result ed in earlier consensus around goals of care for dying trauma patients . Integration of early palliative care alongside aggressive trauma care can be accomplished without change in mortality and has the ability to change the culture of care in the trauma ICU STUDY OBJECTIVES To assess the impact of a proactive case finding approach to end-of-life care for critically ill patients experiencing global cerebral ischemia ( GCI ) after cardiopulmonary resuscitation and multiple organ system failure ( MOSF ) in comparison to historical control subjects . DESIGN Comparative study of retrospective and prospect i ve cohorts . SETTING Medical ICU of a university hospital . INTERVENTIONS Patterns of end-of life care for patients with MOSF and GCI obtained through a retrospective chart review were compared to proactive case finding facilitated by the inpatient palliative care service . Interventions included identification of patient 's advance directives or preferences about end-of life care , if any ; assistance with discussion of the prognosis and treatment options with patients or their surrogates ; and implementation of palliative care strategies when treatment goals changed to a focus on comfort measures . RESULTS Although our retrospective data demonstrated a high percentage of do-not-resuscitate decisions for the patients under investigation , a considerable time lag elapsed between identification of the poor prognosis and the establishment of end-of-life treatment goals ( 4.7 + /- 2.4 days and 3.5 + /- 0.5 days for patients with MOSF and GCI , respectively [ mean + /- SE ] ) . The proactive case finding approach decreased hospital length of stay ( mean , 20.6 + /- 4.1 days vs 15.1 + /- 2.5 days and 8.6 + /- 1.6 days vs 4.7 + /- 0.6 days for MOSF and GCI patients , respectively ; p = 0.063 and < 0.001 , respectively ) . More importantly , a proactive palliative care intervention decreased the time between identification of the poor prognosis and the establishment of comfort care goals ( 7.3 + /- 2.9 days vs 2.2 + /- 0.8 days and 6.3 + /- 1.2 days vs 3.5 + /- 0.4 days for MOSF and GCI patients , respectively ; p < 0.05 for both ) , decreased the time dying patients with MOSF remained in the ICU , and reduced the use of nonbeneficial re sources , thus reducing the cost of care . CONCLUSIONS Proactive interventions from a palliative care consultant within this subset of patients decreased the use of nonbeneficial re sources and avoided protracted dying Objective : To determine if a video depicting cardiopulmonary resuscitation and resuscitation preference options would improve knowledge and decision making among patients and surrogates in the ICU . Design : R and omized , unblinded trial . Setting : Single medical ICU . Patients : Patients and surrogate decision makers in the ICU . Interventions : The usual care group received a st and ard pamphlet about cardiopulmonary resuscitation and cardiopulmonary resuscitation preference options plus routine code status discussion s with clinicians . The video group received usual care plus an 8-minute video that depicted cardiopulmonary resuscitation , showed a simulated hospital code , and explained resuscitation preference options . Measurements and Main Results : One hundred three patients and surrogates were r and omized to usual care . One hundred five patients and surrogates were r and omized to video plus usual care . Median total knowledge scores ( 0–15 points possible for correct answers ) in the video group were 13 compared with 10 in the usual care group , p value of less than 0.0001 . Video group participants had higher rates of underst and ing the purpose of cardiopulmonary resuscitation and resuscitation options and terminology and could correctly name components of cardiopulmonary resuscitation . No statistically significant differences in documented resuscitation preferences following the interventions were found between the two groups , although the trial was underpowered to detect such differences . A majority of participants felt that the video was helpful in cardiopulmonary resuscitation decision making ( 98 % ) and would recommend the video to others ( 99 % ) . Conclusions : A video depicting cardiopulmonary resuscitation and explaining resuscitation preference options was associated with improved knowledge of in-hospital cardiopulmonary resuscitation options and cardiopulmonary resuscitation terminology among patients and surrogate decision makers in the ICU , compared with receiving a pamphlet on cardiopulmonary resuscitation . Patients and surrogates found the video helpful in decision making and would recommend the video to others PURPOSE We sought to determine the effects of a communication process that was design ed to encourage the use of advanced supportive technology when it is of benefit , but to limit its burdens when it is ineffective . We compared usual care with a proactive , multidisciplinary method of communicating that prospect ively identified for patients and families the criteria that would determine whether a care plan was effective at meeting the goals of the patient . This process allowed caregivers to be informed of patient preferences about continued advanced supportive technology when its continuation would result in a compromised functional outcome or death . MATERIAL S AND METHODS We performed a before- and -after study in 530 adult medical patients who were consecutively admitted to a university tertiary care hospital for intensive care . Multidisciplinary meetings were held within 72 hours of critical care admission . Patients , families , and the critical care team discussed the care plan and the patients ' goals and expectations for the outcome of critical care . Clinical " milestones " indicative of recovery were identified with time frames for their occurrence . Follow-up meetings were held to discuss palliative care options when continued advanced supportive technology was not achieving the patient 's goals . We measured length of stay , mortality , and provider team and family consensus in 134 patients before the intensive communication intervention and in 396 patients after the intervention . RESULTS Intensive communication significantly reduced the median length of stay from 4 days ( interquartile range , 2 to 11 days ) to 3 days ( 2 to 6 days , P = 0.01 by survival analysis ) . This reduction remained significant after adjustment for acute physiology and chronic health evaluation ( APACHE ) 3 score [ risk ratio ( RR ) = 0.81 ; 95 % confidence interval ( CI ) , 0.66 to 0.99 ; P = 0.04 ) . Subgroup analysis revealed that this reduction occurred in our target group , patients with acuity scores in the highest quartile who died ( RR = 0.60 ; 95 % CI , 0.38 to 0.92 ; P = 0.02 ) . The intervention , which allowed dying patients earlier access to palliative care , was not associated with increased mortality . CONCLUSIONS Intensive communication was associated with a reduction in critical care use by patients who died . Our multidisciplinary process targeted advanced supportive technology to patients who survived and allowed the earlier withdrawal of advanced supportive technology when it was ineffective Comprehension and satisfaction are relevant criteria for evaluating the effectiveness of information provided to family members of intensive care unit ( ICU ) patients . We performed a prospect i ve r and omized trial in 34 French ICUs to compare comprehension of diagnosis , prognosis , treatment , and satisfaction with information provided by ICU caregivers , in ICU patient family representatives who did ( n = 87 ) or did not ( n = 88 ) receive a family information leaflet ( FIL ) in addition to st and ard information . An FIL design ed specifically for this study was delivered at the first visit of the family representative : it provided general information on the ICU and hospital , the name of the ICU physician caring for the patient , a diagram of a typical ICU room with the names of all the devices , and a glossary of 12 terms commonly used in ICUs . Characteristics of the ICUs , patients , and family representatives were similar in the two groups . The FIL reduced the proportion of family members with poor comprehension from 40.9 % to 11.5 % ( p < 0.0001 ) . In the representatives with good comprehension , the FIL was associated with significantly better satisfaction ( 21 [ 18 to 24 , quartiles ] versus 27 [ 24 to 29 , quartiles ] , p = 0.01 ) . These results indicate that ICU caregivers should consider using an FIL to improve the effectiveness of the information they impart to families Objective To develop , deploy , and evaluate an intervention design ed to identify and mitigate conflict in decision making in the intensive care unit . Design Nonr and omized , controlled trial . Setting Seven intensive care units at four Boston teaching hospitals . Patients A total of 1,752 critically ill patients , including 873 study cases analyzed here . InterventionS ocial workers interviewed families of patients deemed at high risk for decisional conflict and provided feedback to the clinical team , who then implemented measures to address the problems identified . Measurements and Main Results Patient or surrogate satisfaction with intensive care unit care and the probability of choosing a specific plan for treatment in the intensive care unit was studied . Inclusion criteria identified 873 patients at risk for decisional conflict . Thirty-nine percent of the patients in the intervention phase of the study ( 172 patients ) received the intervention . In multivariate analyses , receiving the intervention significantly increased the likelihood of deciding to forgo resuscitation ( odds ratio [ OR ] = 1.81 , p = .017 ) , the likelihood of choosing a treatment plan for comfort-care only ( OR = 1.94 , p = .018 ) , and the likelihood of choosing an aggressive-care treatment plan ( OR = 2.30 , p = .002 ) . Receiving the intervention did not significantly affect overall satisfaction with the care provided ( OR = 0.68 , p = .14 ) , satisfaction with the amount of information provided ( OR = 0.86 , p = .44 ) , or satisfaction with the degree of involvement in decision making ( OR = 0.84 , p = .54 ) . Conclusions Although there was no impact on patient or surrogate satisfaction with care provided in the intensive care unit , the intervention did facilitate deliberative decision making in cases deemed at high risk for conflict . The lessons learned from the experience with this intervention should be helpful in ongoing efforts to improve care and to achieve outcomes desired by critically ill patients , their families , and critical care clinicians In this article two new methods for building and evaluating eHealth interventions are described . The first is the Multiphase Optimization Strategy ( MOST ) . It consists of a screening phase , in which intervention components are efficiently identified for inclusion in an intervention or for rejection , based on their performance ; a refining phase , in which the selected components are fine tuned and issues such as optimal levels of each component are investigated ; and a confirming phase , in which the optimized intervention , consisting of the selected components delivered at optimal levels , is evaluated in a st and ard r and omized controlled trial . The second is the Sequential Multiple Assignment R and omized Trial ( SMART ) , which is an innovative research design especially suited for building time-varying adaptive interventions . A SMART trial can be used to identify the best tailoring variables and decision rules for an adaptive intervention empirically . Both the MOST and SMART approaches use r and omized experimentation to enable valid inferences . When properly implemented , these approaches will lead to the development of more potent eHealth interventions CONTEXT Patients , families , and surgeons often have high expectations of life-saving surgery following liver transplantation ( LT ) , despite the presence of a severe life-limiting underlying illness . Hence , transition from curative to palliative care is difficult and may create conflicts around goals of care . OBJECTIVES We hypothesized that early communication with physicians/families would improve end-of-life care practice in the LT service patients . METHODS Prospect i ve , observational , pre/post study of consecutive LT service , surgical intensive care unit ( SICU ) patients , before and after a palliative care intervention was integrated . This included Part I ( at admission ) , family support , prognosis , and patient preferences delineation ; and Part II ( within 72 hours ) , interdisciplinary family meeting . Data on goals -of-care discussion s , do-not-resuscitate ( DNR ) orders , withdrawal of life support , and family perceptions were collected . RESULTS Seventy-nine LT patients with 21 deaths comprised the baseline group and 104 patients with 31 deaths the intervention group . Eighty-five percent of patients received Part I and 58 % Part II of the intervention . Goals -of-care discussion s on physician rounds increased from 2 % to 38 % of patient-days . During the intervention , although mortality rates were unchanged , DNR status increased ( 52 - 81 % ) ; withdrawal of life support increased ( 35 - 68 % ) ; DNR was instituted earlier ; admission to DNR decreased ( mean of 38 - 19 days ) ; DNR to death time increased ( two to four days ) ; and SICU mean length of stay decreased ( by three days ) . Family responses suggested more " time with family"/"time to say goodbye . " CONCLUSION Interdisciplinary communication interventions with physicians and families result ed in earlier consensus around goals of care for dying LT patients . Early integration of palliative care alongside disease-directed curative care can be accomplished in the SICU without change in mortality and has the ability to improve end-of-life care practice in LT patients CONTEXT Ethics consultations increasingly are being used to resolve conflicts about life-sustaining interventions , but few studies have reported their outcomes . OBJECTIVE To investigate whether ethics consultations in the intensive care setting reduce the use of life-sustaining treatments delivered to patients who ultimately did not survive to hospital discharge , as well as the reactions to the consultations of physicians , nurses , and patients /surrogates . DESIGN Prospect i ve , multicenter , r and omized controlled trial from November 2000 to December 2002 . SETTING Adult intensive care units ( ICUs ) of 7 US hospitals representing a spectrum of institutional characteristics . PATIENTS Five hundred fifty-one patients in whom value-related treatment conflicts arose during the course of treatment . INTERVENTIONS Patients were r and omly assigned either to an intervention ( ethics consultation offered ) ( n = 278 ) or to usual care ( n = 273 ) . MAIN OUTCOME MEASURES The primary outcomes were ICU days and life-sustaining treatments in those patients who did not survive to hospital discharge . We examined the same measures in those who did survive to discharge and also compared the overall mortality rates of the intervention and usual care groups . We also interviewed physicians and nurses and patients /surrogates about their views of the ethics consultation . RESULTS The intervention and usual-care groups showed no difference in mortality . However , ethics consultations were associated with reductions in hospital ( -2.95 days , P = .01 ) and ICU ( -1.44 days , P = .03 ) days and life-sustaining treatments ( -1.7 days with ventilation , P = .03 ) in those patients who ultimately did not survive to discharge . The majority ( 87 % ) of physicians , nurses , and patients /surrogates agreed that ethics consultations in the ICU were helpful in addressing treatment conflicts . CONCLUSION Ethics consultations were useful in resolving conflicts that may have inappropriately prolonged nonbeneficial or unwanted treatments in the ICU OBJECTIVE To assess the effect of proactive ethics consultation on documented patient care communications and on decisions regarding high-risk intensive care unit ( ICU ) patients . DESIGN Prospect i ve , controlled study . PATIENTS Ninety-nine ICU patients treated with > 96 hrs of continuous mechanical ventilation . INTERVENTIONS Three groups were compared : a ) a baseline group enrolled in the study prior to the establishment of the hospital 's ethics consultation service ; b ) a control group where ethics consultation was at the option of the care team ; and c ) a treatment group where the ethics service intervened proactively after patients received > 96 hrs of continuous mechanical ventilation . Patient care planning , for subjects in the proactive group , was review ed with physicians and with the care team using a st and ardized set of prompting questions design ed to focus discussion of key decision-making and communication issues for critically and terminally ill patients . Issues and concerns were identified and action strategies were suggested to those in charge of the patient 's care . Formal ethics consultation , using a patient care conference model , was made available upon request . MEASUREMENTS AND MAIN RESULTS Post discharge chart review s of the three groups indicated no statistically significant differences on important demographic variables including age , gender , and acuity . Comparisons of survivors and nonsurvivors for the three groups indicated , at statistically significant levels , more frequent and documented communications , more frequent decisions to forego life-sustaining treatment , and reduced length of stay in the ICU for the proactive consultation group . CONCLUSION Proactive ethics consultation for high-risk patient population s offers a promising approach to improving decision-making and communication and reducing length of ICU stay for dying patients Objective : Shared decision making is inadequate in intensive care units . Decision aids can improve decision making quality , though their role in an intensive care units setting is unclear . We aim ed to develop and pilot test a decision aid for shared decision makers of patients undergoing prolonged mechanical ventilation . Setting : Intensive care units at three medical centers . Subjects : Fifty-three surrogate decision makers and 58 physicians . Design and Interventions : We developed the decision aid using defined method ological guidelines . After an iterative revision process , formative cognitive testing was performed among surrogate – physician dyads . Next , we compared the decision aid to usual care control in a prospect i ve , before/after design study . Measurements and Main Results : Primary outcomes were physician – surrogate discordance for expected patient survival , comprehension of relevant medical information , and the quality of communication . Compared to control , the intervention group had lower surrogate – physician discordance ( 7 [ 10 ] vs. 43 [ 21 ] ) , greater comprehension ( 11.4 [ 0.7 ] vs. 6.1 [ 3.7 ] ) , and improved quality of communication ( 8.7 [ 1.3 ] vs. 8.4 [ 1.3 ] ) ( all p < .05 ) post-intervention . Hospital costs were lower in the intervention group ( $ 110,609 vs. $ 178,618 ; p = .044 ) ; mortality did not differ by group ( 38 % vs. 50 % , p = .95 ) . Ninety-four percent of the surrogates and 100 % of the physicians reported that the decision aid was useful in decision making . Conclusion : We developed a prolonged mechanical ventilation decision aid that is feasible , acceptable , and associated with both improved decision-making quality and less re source utilization . Further evaluation using a r and omized controlled trial design is required to evaluate the decision aid ’s effect on long-term patient and surrogate outcomes OBJECTIVES To improve end-of-life decision making and reduce the frequency of a mechanically supported , painful , and prolonged process of dying . DESIGN A 2-year prospect i ve observational study ( phase I ) with 4301 patients followed by a 2-year controlled clinical trial ( phase II ) with 4804 patients and their physicians r and omized by specialty group to the intervention group ( n = 2652 ) or control group ( n = 2152 ) . SETTING Five teaching hospitals in the United States . PATIENTS A total of 9105 adults hospitalized with one or more of nine life-threatening diagnoses ; an overall 6-month mortality rate of 47 % . INTERVENTION Physicians in the intervention group received estimates of the likelihood of 6-month survival for every day up to 6 months , outcomes of cardiopulmonary resuscitation ( CPR ) , and functional disability at 2 months . A specifically trained nurse had multiple contacts with the patient , family , physician , and hospital staff to elicit preferences , improve underst and ing of outcomes , encourage attention to pain control , and facilitate advance care planning and patient-physician communication . RESULTS The phase I observation documented shortcomings in communication , frequency of aggressive treatment , and the characteristics of hospital death : only 47 % of physicians knew when their patients preferred to avoid CPR : 46 % of do-not-resuscitate ( DNR ) orders were written within 2 days of death ; 38 % of patients who died spent at least 10 days in an intensive care unit ( ICU ) ; and for 50 % of conscious patients who died in the hospital , family members reported moderate to severe pain at least half the time . During the phase II intervention , patients experienced no improvement in patient-physician communication ( eg , 37 % of control patients and 40 % of intervention patients discussed CPR preferences ) or in the five targeted outcomes , ie , incidence or timing of written DNR orders ( adjusted ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.90 to 1.15 ) , physicians ' knowledge of their patients ' preferences not to be resuscitated ( adjusted ratio , 1.22 ; 95 % CI , 0.99 to 1.49 ) , number of days spent in an ICU , receiving mechanical ventilation , or comatose before death ( adjusted ratio , 0.97 ; 95 % CI , 0.87 to 1.07 ) , or level of reported pain ( adjusted ratio , 1.15 ; 95 % CI , 1.00 to 1.33 ) . The intervention also did not reduce use of hospital re sources ( adjusted ratio , 1.05 ; 95 % CI , 0.99 to 1.12 ) . CONCLUSIONS The phase I observation of SUPPORT confirmed substantial shortcomings in care for seriously ill hospitalized adults . The phase II intervention failed to improve care or patient outcomes . Enhancing opportunities for more patient-physician communication , although advocated as the major method for improving patient outcomes , may be inadequate to change established practice s. To improve the experience of seriously ill and dying patients , greater individual and societal commitment and more proactive and forceful measured may be needed BACKGROUND Chronic critical illness is a devastating syndrome of prolonged respiratory failure and other derangements . To our knowledge , no previous research has addressed brain dysfunction in the chronically critically ill , although this topic is important for medical decision making . METHODS We studied a prospect i ve cohort of 203 consecutive , chronically critically ill adults transferred to our hospital 's respiratory care unit ( RCU ) after tracheotomy for failure to wean . We measured prevalence and duration of coma and delirium during RCU treatment using the Confusion Assessment Method for the Intensive Care Unit with the Richmond Agitation-Sedation Scale . To assess survivors ( at 3 and 6 months after RCU discharge ) , we used a vali date d telephone Confusion Assessment Method . RESULTS Before hospitalization , most ( 153 [ 75.4 % ] ) of the 203 patients in the study were at home , completely independent ( 115 [ 56.7 % ] ) , and cognitively intact ( 116 [ 82.0 % ] ) . In the RCU , 61 ( 30.0 % ) were comatose throughout the stay . Approximately half of patients ( 66 of 142 ) who were not in coma were delirious . Patients spent an average of 17.9 days ( range , 1 - 153 days ) in coma or delirium ( average RCU stay , 25.6 days ) . Half of survivors ( 79 of 160 ) had one of these disturbances at RCU discharge . At 6 months , three fourths ( 151 ) of the study patients were dead or institutionalized ; of 85 survivors , 58 ( 68.2 % ) were too profoundly impaired to respond to telephone cognitive assessment , and 53 ( 62.4 % ) were dependent in all activities of daily living . CONCLUSIONS Severe , prolonged , and permanent brain dysfunction is a prominent feature of chronic critical illness . These data , together with previous reports of symptom distress and rates of mortality and institutionalization , describe burdens for chronically critically ill patients receiving continued life-prolonging treatment and for their families BACKGROUND There is a need for close communication with relatives of patients dying in the intensive care unit ( ICU ) . We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement . METHODS Family members of 126 patients dying in 22 ICUs in France were r and omly assigned to the intervention format or to the customary end-of-life conference . Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale ( IES ; scores range from 0 , indicating no symptoms , to 75 , indicating severe symptoms related to post-traumatic stress disorder [ PTSD ] ) and the Hospital Anxiety and Depression Scale ( HADS ; subscale scores range from 0 , indicating no distress , to 21 , indicating maximum distress ) . RESULTS Participants in the intervention group had longer conferences than those in the control group ( median , 30 minutes [ interquartile range , 19 to 45 ] vs. 20 minutes [ interquartile range , 15 to 30 ] ; P<0.001 ) and spent more of the time talking ( median , 14 minutes [ interquartile range , 8 to 20 ] vs. 5 minutes [ interquartile range , 5 to 10 ] ) . On day 90 , the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group ( 27 vs. 39 , P=0.02 ) and a lower prevalence of PTSD-related symptoms ( 45 % vs. 69 % , P=0.01 ) . The median HADS score was also lower in the intervention group ( 11 , vs. 17 in the control group ; P=0.004 ) , and symptoms of both anxiety and depression were less prevalent ( anxiety , 45 % vs. 67 % ; P=0.02 ; depression , 29 % vs. 56 % ; P=0.003 ) . CONCLUSIONS Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement . ( Clinical Trials.gov number , NCT00331877 . Objective : The purpose of this study was to examine the effect of proactive palliative care consultation on length of stay for high-risk patients in the medical intensive care unit ( MICU ) . Design : A prospect i ve pre/post nonequivalent control group design was used for this performance improvement study . Setting : Seventeen-bed adult MICU . Patients : Of admissions to the MICU , 191 patients were identified as having a serious illness and at high risk of dying : 65 patients in the usual care phase and 126 patients in the proactive palliative care phase . To be included in the sample , a patient had to meet one of the following criteria : a ) intensive care admission following a current hospital stay of ≥10 days ; b ) age > 80 yrs in the presence of two or more life-threatening comorbidities ( e.g. , end-stage renal disease , severe congestive heart failure ) ; c ) diagnosis of an active stage IV malignancy ; d ) status post cardiac arrest ; or e ) diagnosis of an intracerebral hemorrhage requiring mechanical ventilation . Interventions : Palliative care consultations . Measurements and Main Results : Primary measures were patient lengths of stay a ) for the entire hospitalization ; b ) in the MICU ; and c ) from MICU admission to hospital discharge . Secondary measures included mortality rates and discharge disposition . There were no significant differences between the usual care and proactive palliative care intervention groups in respect to age , gender , race , screening criteria , discharge disposition , or mortality . Patients in the proactive palliative care group had significantly shorter lengths of stay in the MICU ( 8.96 vs. 16.28 days , p = .0001 ) . There were no differences between the two groups on total length of stay in the hospital or length of stay from MICU admission to hospital discharge . Conclusions : Proactive palliative care consultation was associated with a significantly shorter MICU length of stay in this high-risk group without any significant differences in mortality rates or discharge disposition Objective Effective communication of simple , clear information to families of intensive care unit ( ICU ) patients is a vital component of quality care . The purpose of this study was to identify factors associated with poor comprehension by family members of the status of ICU patients . Design Prospect i ve study . Setting University-affiliated medical intensive care unit . Patients and Methods A total of 102 patients admitted to an ICU for > 2 days . InterventionThe representatives of 76 patients who were visited by at least one person during their ICU stay were interviewed . Results Mean patient age was 54 ± 17 yrs and mean Simplified Acute Physiology Score II at admission was 40 ± 20 . The representative was the spouse in 47 cases ( 62 % ) . Among representatives , 25 ( 33 % ) were of foreign descent and 12 ( 16 % ) did not speak French . Mean duration of the first meeting with a physician was 10 ± 6 mins . In 34 cases ( 54 % ) , the representative failed to comprehend the diagnosis , prognosis , or treatment of the patient . Factors associated with poor comprehension by representatives included patient-related , family-related , and physician- related factors . Patient-related factors included age < 50 yrs ( p = .03 ) , unemployment ( p = .01 ) , referral from a hematology or oncology ward ( p = .006 ) , admission for acute respiratory failure ( p = .005 ) or coma ( p = .01 ) , and a relatively favorable prognosis ( p = .04 ) . Family-related factors were foreign descent ( p = .007 ) , no knowledge of French ( p = .03 ) , representative not the spouse ( p = .03 ) , and no healthcare professional in the family ( p = .01 ) . Physician-related factors were first meeting with representative < 10 mins ( p = .03 ) and failure to give the representative an information brochure ( p = .02 ) . Moreover , after the first meeting , caregivers accurately predicted poor comprehension by representatives ( p = .03 ) . Conclusions Patient information is frequently not communicated effectively to family members by ICU physicians . Physicians should strive to identify patients and families who require special attention and to determine how their personal style of interrelating with family members may impair communication |
429 | 23,380,943 | There was evidence of a nonlinear association between red meat ( pnonlinearity < 0.001 ) and processed meat ( pnonlinearity = 0.01 ) intake and colorectal adenoma risk . | Background Current evidence indicates that red and processed meat intake increases the risk of colorectal cancer ; however , the association with colorectal adenomas is unclear .
Objective To conduct a systematic review and meta- analysis of epidemiological studies of red and processed meat intake and risk of colorectal adenomas as part of the Continuous Up date Project of the World Cancer Research Fund . | Some serrated polyps of the colorectum are likely preinvasive lesions , evolving through a newly recognized serrated pathway to colorectal cancer . To assess possible risk and protective factors for serrated polyps and particularly to explore differences in risk factors between polyps in the right and left colorectum , we pooled data from three large multicenter chemoprevention trials . A serrated polyp was defined broadly as any serrated lesion ( hyperplastic , sessile serrated adenoma , “ traditional ” serrated adenoma , mixed adenoma ) diagnosed during each trial 's main treatment period of ∼3 to 4 years . Using generalized linear regression , we computed risk ratios and 95 % confidence intervals as measures of the association between risk for serrated polyps and demographic , lifestyle , and dietary variables . Of the 2,830 subjects that completed at least one follow-up exam after r and omization , 675 ( 23.9 % ) had at least one left-sided serrated polyp and 261 ( 9.2 % ) had at least one right-sided lesion . In the left colorectum , obesity , cigarette smoking , dietary fat , total energy intake , and red meat intake were associated with an increased risk for serrated polyps . In the right colon , aspirin treatment was associated with a reduced risk and family history of polyps and folate treatment were associated with an increased risk for serrated polyps . Our results suggest that several common lifestyle and dietary variables are associated with risk for serrated polyps , and some of these may differ for the right and left colorectum . ( Cancer Epidemiol Biomarkers Prev 2009;18(8):2310–7 OBJECTIVE : The aim of this study was to determine the relationship between fat , fiber , and meat intake , and risk of colorectal adenoma recurrence . METHODS : We determined adenoma recurrence and dietary intake for 1,520 participants in two r and omized trials : The Antioxidant Polyp Prevention Study and Calcium Polyp Prevention Study . Subjects underwent baseline colonoscopy with removal of all adenomas , and dietary intake was estimated with a vali date d semiquantitative food frequency question naire . Follow-up colonoscopy was performed 1 and 4 yr later . Pooled risk ratios for adenoma recurrence were obtained by generalized linear regression , with adjustment for age , sex , clinical center , treatment category , study , and duration of observation . RESULTS : In the total colorectum , fiber intake was weakly and nonsignificantly associated with a risk for all adenomas ( RR quartile 4 vs quartile 1 = 0.85 , 95 % CI 0.69–1.05 ) and advanced adenomas ( RR = 0.88 , 95 % CI 0.54–1.44 ) . Associations were stronger for adenomas in the proximal colon ( RR = 0.73 , 95 % CI 0.56–0.97 ) and some fiber subtypes ( fruit and vegetable , grain ) . There was no association between fat or total red meat intake and risk of adenoma or advanced adenoma recurrence . However , when considering other meats , risk ( quartile 4 vs quartile 1 ) for advanced adenoma was increased for processed meat ( RR = 1.75 , 95 % CI 1.02–2.99 ) and decreased for chicken ( RR = 0.61 , 95 % CI 0.38–0.98 ) . CONCLUSION : The inverse associations between fiber intake and risk of adenoma recurrence we observed are weak , and not statistically significant . Our data indicate that intake of specific meats may have different effects on risk Many N-nitroso compounds ( NOC ) are carcinogens . In this controlled study of 21 healthy male volunteers , levels of NOC on a high ( 420 grams ) red meat diet were significantly greater ( P = 0.001 ) than on a low ( 60 grams ) meat diet but not significantly greater when an equivalent amount of vegetable protein was fed . An 8-mg supplement of haem iron also increased fecal NOC ( P = 0.006 ) compared with the low meat diet , but 35-mg ferrous iron had no effect . Endogenous N-nitrosation , arising from ingestion of haem but not inorganic iron or protein , may account for the increased risk associated with red meat consumption in colorectal cancer Cooking meats at high temperatures and for long duration produces heterocyclic amines and other mutagens . These meat-derived mutagenic compounds have been hypothesized to increase risk of colorectal neoplasia , but prospect i ve data are unavailable . We examined the association between intakes of the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5,-f]quinoxaline ( MeIQx ) , 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline ( DiMeIQx ) , and meat-derived mutagenicity ( MDM ) and risk of distal colon adenoma using a cooking method question naire administered in 1996 in the Health Professionals Follow-up Study cohort . Between 1996 and 2002 , 581 distal colon adenoma cases were identified . Higher intake of MDM was marginally associated with increased risk of distal adenoma [ fourth versus lowest quintile : odds ratio ( OR ) , 1.39 ; 95 % confidence interval ( 95 % CI ) , 1.05 - 1.84 ; highest versus lowest quintile : OR , 1.29 ; 95 % CI , 0.97 - 1.72 ; Ptrend = 0.08 ] . Adjusting for total red meat or processed meat intake did not explain those associations . Our data also suggested a positive association between higher MeIQx ( highest versus lowest quintile : OR , 1.28 ; 95 % CI , 0.95 - 1.71 ; Ptrend = 0.22 ) and risk of adenoma , but this association was attenuated after adjusting for processed meat intake . DiMeIQx and PhIP did not seem to be associated with risk of adenoma . In conclusion , higher consumption of mutagens from meats cooked at higher temperature and longer duration may be associated with higher risk of distal colon adenoma independent of overall meat intake . Because mutagens other than heterocyclic amines also contribute to MDM , our results suggest that mutagens other than heterocyclic amines in cooked meats may also play a role in increasing the risk of distal adenoma . ( Cancer Epidemiol Biomarkers Prev 2006;15(6):1120–5 Diet has long been thought to be an important factor in the etiology of colorectal cancer . The specific dietary nutrients or factors responsible for this disease , the second leading cause of cancer death in the United States [ 1 ] , have not , however , been clearly eluci date d. Colorectal adenomatous polyps ( here referred to as polyps ) are generally considered to be precursor lesions for most cases of colorectal carcinoma [ 2 - 4 ] ; however , little is known about their risk factors . Since the introduction of fiberoptic endoscopy , especially colonoscopy , attention has focused on the potential for preventing colorectal cancer by screening for and resecting the adenomas [ 5 , 6 ] . Because of their high recurrence rate after resection [ 7 , 8 ] , these polyps have been used as an end point for the study of potential chemopreventive agents . Four studies have explored potential dietary risk factors for incident colorectal adenomatous polyps [ 9 - 12 ] . No previous observational studies have explored the role of diet or other lifestyle factors in the recurrence of polyps after polypectomy . We discuss the results of a casecontrol study of colorectal polyps among patients from three colonoscopy practice s and analyze dietary risk factors for both incident and recurrent polyps . Methods Our study sample included patients having colonoscopy at three colonoscopy practice s in New York City between April 1986 and March 1988 . In total , 2988 patients were evaluated . Of these , 2443 ( 81.8 % ) were eligible for our study ( patients had to be between 35 and 84 years of age ; reside in New York , New Jersey , or Connecticut ; speak English or Spanish ; and have colonoscopy to at least the splenic flexure ) . The colonoscopists completed data sheets indicating the reason for colonoscopy and the clinical findings at the time of colonoscopy . The study pathologist review ed slides of all suspected neoplastic lesions . All eligible participants received a letter signed by their colonoscopist introducing the study . A trained interviewer then contacted and interviewed participants by telephone . Alternatively , the question naire was mailed for self-completion and was followed by a telephone interview to resolve any remaining questions . An earlier study indicated that the results obtained for dietary factors were similar for both interview methods [ 13 ] . The interview itself consisted of a general question naire that focused on demographic characteristics , medical history , lifestyle , family history , and other topics . The dietary interview consisted of the Block food frequency question naire and specified food intake for a period 3 to 5 years before the colonoscopy [ 14 ] . Ultimately , 1956 dietary question naires were completed ( 80.1 % of eligible patients ) . Of these , 71 % were conducted by telephone , and 29 % were returned by mail . An incident case of adenomatous polyps was defined as an eligible participant with no history of colon carcinoma , adenomatous polyps , or inflammatory bowel disease who was found to have one or more pathologically defined polyps on the index colonoscopy . The incident control group consisted of persons who were found to be free of colorectal neoplasia on index colonoscopy and who were without a history of adenomatous polyps , colon cancer , or inflammatory bowel disease . A case of recurrent polyps was defined as an eligible participant with a self-reported history of one or more polyps who had a pathologically confirmed polyp on the index colonoscopy . The recurrent control was defined as a participant whose index colonoscopy showed no colorectal neoplasia but who had a history of one or more polyps . Cases and controls with a history of colorectal cancer or inflammatory bowel disease were excluded . Although we did not have pathologic confirmation of all initial polyps , we did obtain pathology reports on a r and om sample of 100 recurrent cases and controls and found 97 to be adenomatous . By these criteria , 286 incident cases ( 162 men and 124 women ) and 480 incident controls ( 210 men and 270 women ) were identified , whereas 186 recurrence cases ( 130 men and 56 women ) and 330 recurrence controls ( 187 men and 143 women ) were found . Food item and nutrient data were generated by software programs provided by Block and coworkers [ 14 ] at the National Cancer Institute . The main analyses were done using logistic regression modelling and maximum likelihood ratios [ 15 ] in the BMDP-LR program . Analyses were conducted separately for men and women . Age , Quetelet index , and caloric intake were entered as covariates for most analyses . A previous study by our group had shown obesity , as measured by Quetelet index , to be a risk factor for polyps among women ; the trend for men was not significant [ 16 ] . Analyses in which nutrients were st and ardized per 1000 kilocalories were also done for comparison [ 17 ] . For each nutrient or food group , quartiles were defined by review of the control group data ; the lowest quartile was given a reference value of 1.0 , and odds ratios were calculated for each of the other quartiles , with 95 % confidence intervals ( CIs ) for the highest-to-lowest quartile comparison . The probability of a linear trend was calculated by entering the four quartiles as ordered categories . Results The case and control groups for the incidence and recurrence studies were generally similar in age distribution and education . Table 1 shows a comparison of the characteristics of the case and control groups for both the incident and recurrent groups . Most polyps were 5 mm or larger in size and had at least some degree of atypia . The site distribution of the incident polyps showed a preponderance to the left . Most incident case and control participants had colonoscopy because of overt or occult rectal bleeding . A larger proportion of the recurrent polyps were right-sided ( P = 0.005 ) . The time interval from initial polypectomy to index colonoscopy was 4.3 years for cases and 3.7 years for controls ( P > 0.2 ) . Table 1 . Polyp Characteristics for Incident and Recurrent Cases Tables 2 and 3 show the odds ratios by quartile , using the lowest quartile as the referent group , for some of the 15 nutrients and food groups evaluated . The results for vegetables , red meat , beef , cheese , protein , vitamin C , and carotene are not shown ; however , no consistent differences were found . Table 2 . Odds Ratios of Incident Polyps by Quartile of Selected Nutrients and Food Groups , Adjusted for Age , Quetelet Index , and Caloric Intake Table 3 . Odds Ratios of Recurrent Polyps by Quartile of Selected Nutrients and Food Groups , Adjusted for Age , Quetelet Index , and Caloric Intake Men The only dietary risk factor statistically associated with the risk for colorectal adenomatous polyps in men was caloric intake ; however , this association was in a direction opposite to that ordinarily expected [ 18 ] . Women In contrast , various dietary factors were observed to be associated with the risk for colorectal adenomatous polyps in women ( Tables 2 and 3 ) . Increased saturated fat , decreased fish and chicken , increased meat-to-fish and -chicken ratio , and decreased vitamin A intake increased the risk for incident polyps ( Table 2 ) . Increased caloric intake , increased total fat , increased saturated fat , and decreased fiber intake all raised the risk for recurrent polyps in women , whereas vitamin A and carbohydrate intake had borderline protective effects ( Table 3 ) . Analyses were also done using nutrient density ( nutrient compared with caloric intake ) instead of entering calories as a covariate . The results are not shown , but the same risk factors were statistically significant for incident polyps in women , although the estimated odds ratios were larger . In addition , fiber was protective for incident polyps in women ( odds ratio , 0.6 ; CI , 0.3 to 1.1 ; P = 0.06 ) . The same dietary factors were also associated with recurrent polyps in women , although the odds ratio estimates were again larger . Both vitamin A ( odds ratio , 0.5 ; CI , 0.2 to 1.1 ; P = 0.06 ) and carbohydrate intake ( odds ratio , 0.4 ; CI , 0.2 to 1.0 ; P = 0.001 ) were more clearly protective . Subgroup Analyses For each of the dietary factors associated with colorectal polyps in women , further subgroup analyses were done for right-sided polyps only , for left-sided polyps only , and for polyps 5 mm or larger in size . Generally , no major variations were observed for the various subgroups , although some reduction was seen in statistical power because of the smaller number of cases . To determine the independent effect of each of the variables found to be associated with polyps in women , we conducted further multiple logistic regression analyses using various dietary factors as covariates . The elevated risk associated with increased consumption of saturated fats remained after adjustment for fiber or vitamin A. Discussion Many studies have suggested that diet plays a role in the etiology of colorectal cancer [ 19 - 35 ] . Evidence suggests that increased consumption of saturated fat is a causal factor and that increased consumption of fiber , ( particularly fruit and vegetable fiber ) is protective [ 26 ] . Similarly , an increased risk has been associated with greater consumption of red meat compared with chicken or fish [ 19 ] , and a protective effect has been linked to consumption of vegetables [ 35 ] . A protective effect of such micronutrients as vitamin A , carotene [ 32 - 34 ] , and calcium [ 27 - 30 ] has also been suggested , although the evidence is less compelling . Because adenomatous polyps are known precursors for colorectal cancer , three casecontrol studies [ 9 - 11 ] have explored their association with diet . Despite their limitations , each study has suggested a protective effect for fiber . A recent cohort study [ 12 ] of male health professionals found saturated fat and decreased fiber , as well as increased red meat-to-fish and meat-to-chicken ratio , to be risk factors for left-sided incident polyps . A small study by our group also showed that supplemental vitamins had no influence on the development Red meat consumption has been positively associated with colorectal cancer ; however , the biological mechanism underlying this relationship is not understood . Red meat is a major source of iron , which may play a role in colorectal carcinogenesis via increased crypt cell proliferation , cytotoxicity , and endogenous N-nitrosation . In a nested case – control study within the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , we prospect ively evaluated multiple iron exposure parameters , including dietary intake and serum measures of iron , ferritin , transferrin , total iron binding capacity ( TIBC ) , and unsaturated iron binding capacity ( UIBC ) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls . We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls . We observed a positive association between red meat intake and colorectal adenoma [ OR comparing extreme quartiles ( ORq4-q1 ) = 1.59 , 95 % CI = 1.02–2.49 , Ptrend = 0.03 ] . Serum TIBC and UIBC were inversely associated with colorectal adenoma ( ORq4-q1 = 0.57 , 95 % CI = 0.37–0.88 , Ptrend = 0.03 ; and ORq4-q1 = 0.62 , 95 % CI = 0.40–0.95 , Ptrend = 0.04 , respectively ) . Colorectal adenoma was not associated with serum ferritin , iron , or transferrin saturation or with polymorphisms in genes involved in iron homeostasis . Serum TIBC and UIBC , parameters that have a reciprocal relationship with overall iron load , were inversely related to colorectal adenoma , suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma . Cancer Prev Res ; 4(9 ) ; 1465–75 . © 2011 AACR BACKGROUND Colorectal cancer is the third most common cancer worldwide and has a high mortality rate . We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality . METHODS This r and omised controlled trial was undertaken in 14 UK centres . 170 432 eligible men and women , who had indicated on a previous question naire that they would accept an invitation for screening , were r and omly allocated to the intervention group ( offered flexible sigmoidoscopy screening ) or the control group ( not contacted ) . R and omisation by sequential number generation was done central ly in blocks of 12 , with stratification by trial centre , general practice , and household type . The primary outcomes were the incidence of colorectal cancer , including prevalent cases detected at screening , and mortality from colorectal cancer . Analyses were intention to treat and per protocol . The trial is registered , number IS RCT N28352761 . FINDINGS 113 195 people were assigned to the control group and 57 237 to the intervention group , of whom 112 939 and 57 099 , respectively , were included in the final analyses . 40 674 ( 71 % ) people underwent flexible sigmoidoscopy . During screening and median follow-up of 11.2 years ( IQR 10.7 - 11.9 ) , 2524 participants were diagnosed with colorectal cancer ( 1818 in control group vs 706 in intervention group ) and 20 543 died ( 13 768 vs 6775 ; 727 certified from colorectal cancer [ 538 vs 189 ] ) . In intention-to-treat analyses , colorectal cancer incidence in the intervention group was reduced by 23 % ( hazard ratio 0.77 , 95 % CI 0.70 - 0.84 ) and mortality by 31 % ( 0.69 , 0.59 - 0.82 ) . In per- protocol analyses , adjusting for self- selection bias in the intervention group , incidence of colorectal cancer in people attending screening was reduced by 33 % ( 0.67 , 0.60 - 0.76 ) and mortality by 43 % ( 0.57 , 0.45 - 0.72 ) . Incidence of distal colorectal cancer ( rectum and sigmoid colon ) was reduced by 50 % ( 0.50 , 0.42 - 0.59 ; secondary outcome ) . The numbers needed to be screened to prevent one colorectal cancer diagnosis or death , by the end of the study period , were 191 ( 95 % CI 145 - 277 ) and 489 ( 343 - 852 ) , respectively . INTERPRETATION Flexible sigmoidoscopy is a safe and practical test and , when offered only once between ages 55 and 64 years , confers a substantial and longlasting benefit . FUNDING Medical Research Council , National Health Service R&D , Cancer Research UK , KeyMed BACKGROUND Heterocyclic aromatic amines ( HCAs ) , which arise from cooking meat and fish at high temperatures , may increase the risk of colorectal adenomas . Conversely , flavonoids might counteract the negative effects of HCAs . OBJECTIVE The association between dietary HCA intake and colorectal adenoma incidence was investigated in a prospect i ve cohort study . DESIGN At recruitment ( 1994 - 1998 ) , detailed information on diet , anthropometric measures , lifestyle , and medication use was assessed in 25,540 participants of the European Prospect i ve Investigation into Cancer and Nutrition-Heidelberg cohort study . Dietary HCA intake was estimated by using information from food-frequency question naires on meat consumption , applied cooking methods , and preferred degree of browning . Until June 2007 , 516 verified incident colorectal adenomas were identified . Participants with negative colonoscopy ( n = 3966 ) were also included in the analytic cohort . Multivariate Cox proportional hazards regression was used to examine the association between colorectal adenoma risk and intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline ( MeIQx ) , and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline ( DiMeIQx ) . RESULTS In multivariate analyses , the intake of PhIP as the most abundant dietary HCA was associated with an increased risk of colorectal adenoma ( relative risk : 1.47 ; 95 % CI : 1.13 , 1.93 ; quartile 4 compared with quartile 1 ; P for trend = 0.002 ) , but no statistically significant associations were observed for MeIQx and DiMeIQx intakes . In addition , adenoma risk also increased with the consumption of strongly or extremely browned meat ( P for trend = 0.04 ) . The association of PhIP intake with adenoma risk was most pronounced for small adenomas ( P for trend = 0.01 ) and adenomas localized in the distal colon ( P for trend = 0.002 ) . CONCLUSION The results of this first European cohort study support data from case-control studies of a positive association between HCA intake and colorectal adenoma risk Red meat intake has been shown to be associated with higher risk of colorectal cancer . Though the exact mechanisms responsible for this association remain unknown , several tumorigenic properties of meat have been proposed . One well-supported biologic mechanism is elevated exposure to the genotoxic formation of heterocyclic amines ( HCAs ) , which occur when meat is cooked at high temperatures for a long period of time . We prospect ively assessed the relation between type of meat , meat preparation method , doneness , a metric of HCAs and other mutagens and colorectal adenoma recurrence among 869 participants in a chemoprevention trial of ursodeoxycholic acid . Unconditional logistic regression analyses were used to estimate odds ratios ( ORs ) and associated 95 % confidence intervals ( CIs ) . Most meat variables assessed were positively but weakly associated with recurrence of any adenoma . In contrast , recurrence of advanced or multiple adenomas was more strongly associated with a number of the meat exposure variables evaluated . For recurrence of advanced lesions , significant associations were detected among individuals in the highest when compared with the lowest tertile of intake for pan-fried red meat ( OR = 1.85 ; 95 % CI = 1.10 - 3.13 ) and well/very well done red meat ( OR = 1.71 ; 95 % CI = 1.02 - 2.86 ) . Significant positive associations were shown for recurrence of multiple adenomas and the following variables : processed meat ( OR = 1.83 ; 95 % CI = 1.10 - 3.04 ) , pan-fried red meat ( OR = 1.63 ; 95 % CI = 1.01 - 2.61 ) , well/very well done red meat ( OR = 1.68 ; 95 % CI = 1.03 - 2.74 ) , 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline ( OR = 1.74 ; 95 % CI = 1.07 - 2.82 ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline ( OR = 1.68 ; 95 % CI = 1.03 - 2.75 ) . Our results support a meat mutagen exposure hypothesis as a potential mechanism for recurrence of clinical ly significant adenomatous polyps BACKGROUND Rates of colorectal cancer in various countries are strongly correlated with per-capita consumption of red meat and animal fat and inversely associated with fiber consumption . There have been few studies , however , of dietary risk factors for colorectal adenomas , which are precursors of cancer . PURPOSE Our purpose was to determine prospect ively the relationship between dietary factors and risk of colorectal adenomas . METHODS Using data from the Health Professionals Follow-up Study , we documented 170 cases of adenomas of the left colon or rectum in 7284 male health professionals who completed a food-frequency question naire in 1986 and who had a colonoscopy or sigmoidoscopy between 1986 and 1988 . Relative risk ( RR ) of adenoma was determined according to quintiles of nutrient intakes . RESULTS After adjustment for total energy intake , saturated fat was positively associated with risk of colorectal adenoma ( P for trend = .006 ) ; RR for the highest versus the lowest quintile of intake was 2.0 ( 95 % confidence interval [ CI ] = 1.2 - 3.2 ) . Dietary fiber was inversely associated with risk of adenoma ( P for trend less than .0001 ) ; RR for men in the highest versus the lowest quintile was 0.36 ( 95 % CI = 0.22 - 0.60 ) . All sources of fiber ( vegetables , fruits , and grains ) were associated with decreased risk of adenoma . For subjects on a high-saturated fat , low-fiber diet , the RR was 3.7 ( 95 % CI = 1.5 - 8.8 ) compared with those on a low-saturated fat , high-fiber diet . The ratio of the intake of red meat to the intake of chicken and fish was positively associated with risk of adenoma ( P for trend = .02 ) . CONCLUSIONS These prospect i ve data provide evidence for the hypothesis that a diet high in saturated fat and low in fiber increases the risk of colorectal adenoma . They also support existing recommendations to substitute chicken and fish for red meat in the diet and to increase intake of vegetables , fruits , and grains to reduce risk of colorectal cancer Previous research suggests that iron acts as a prooxidant to increase the risk of colorectal neoplasia . This study examined effects of dietary intake of iron on colorectal adenoma recurrence using data from an antioxidant clinical trial . All subjects were free of polyps at study entry but had at least one adenoma removed within the 3 months before enrollment . Follow-up colonoscopies were conducted after 1 and 4 years . Patients who developed one or more adenomatous polyps between years 1 and 4 were classified as cases ; all others were controls . Dietary iron intake at baseline and at the end of the study was estimated from self-administered food frequency question naires and averaged together for each subject , energy-adjusted , and categorized into quartiles . Odds ratios were adjusted for age , center , sex , calories , treatment group , and alcohol , fiber , folate , and fat intakes in unconditional logistic regression analysis . Dietary iron was inversely associated with adenoma risk , although risk did not decrease monotonically with increasing intake . Odds ratios comparing second , third , and fourth quartiles to the lowest quartile were 0.61 [ 95 % confidence interval ( CI ) , 0.37 - 1.02 ] , 0.80 ( 95 % CI , 0.45 - 1.44 ) , and 0.37 ( 95 % CI , 0.19 - 0.73 ) , respectively . A limited examination showed no clear evidence that use of iron supplements affected risk of recurrence in this study population . This study provides evidence against the hypothesis that recent dietary intake of iron increases risk for colorectal adenomas . However , these results may reflect the presence of other dietary factors found in combination with iron CONTEXT Knowledge of risk factors for colorectal neoplasia could inform risk reduction strategies for asymptomatic individuals . Few studies have evaluated risk factors for advanced colorectal neoplasia in asymptomatic individuals , compared risk factors between persons with and without polyps , or included most purported risk factors in a multivariate analysis . OBJECTIVE To determine risk factors associated with advanced colorectal neoplasia in a cohort of asymptomatic persons with complete colonoscopy . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , cross-sectional study of 3121 asymptomatic patients aged 50 to 75 years from 13 Veterans Affairs medical centers conducted between February 1994 and January 1997 . All participants had complete colonoscopy to determine the prevalence of advanced neoplasia , defined as an adenoma that was 10 mm or more in diameter , a villous adenoma , an adenoma with high- grade dysplasia , or invasive cancer . Variables examined included history of first-degree relative with colorectal cancer , prior cholecystectomy , serum cholesterol level , physical activity , smoking , alcohol use , and dietary factors . MAIN OUTCOME MEASURES An age-adjusted analysis was performed for each variable to calculate the odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) associated with having advanced neoplasia compared with having no polyps . We developed a multivariate logistic regression model to identify the most informative risk factors . A secondary analysis examined risk factors for having hyperplastic polyps compared with having no polyps and compared with having advanced neoplasia . RESULTS Three hundred twenty-nine participants had advanced neoplasia and 1441 had no polyps . In multivariate analyses , we found positive associations for history of a first-degree relative with colorectal cancer ( OR , 1.66 ; 95 % CI , 1.16 - 2.35 ) , current smoking ( OR , 1.85 ; 95 % CI , 1.33 - 2.58 ) , and current moderate to heavy alcohol use ( OR , 1.02 ; 95 % CI , 1.01 - 1.03 ) . Inverse associations were found for cereal fiber intake ( OR , 0.95 ; 95 % CI , 0.91 - 0.99 ) , vitamin D intake ( OR , 0.94 ; 95 % CI , 0.90 - 0.99 ) , and use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) ( OR , 0.66 ; 95 % CI , 0.48 - 0.91 ) . In the univariate analysis , the inverse association was found with cereal fiber intake greater than 4.2 g/d , vitamin D intake greater than 645 IU/d , and daily use of NSAIDs . Marginal factors included physical activity , daily multivitamin use , and intake of calcium and fat derived from red meat . No association was found for body mass index , prior cholecystectomy , or serum cholesterol level . Three hundred ninety-one patients had hyperplastic polyps as the worst lesion found at colonoscopy . Risk variables were similar to those for patients with no polyps , except that past and current smoking were associated with an increased risk of hyperplastic polyps . CONCLUSIONS Our data endorse several important risk factors for advanced colonic neoplasia and provide a rationale for prudent risk reduction strategies . Further study is needed to determine if lifestyle changes can moderate the risk of colorectal cancer BACKGROUND Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis , but human data for this role have been conflicting , possibly because of problems related to study design or measurement of iron exposure . We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospect i ve , nested case-control study of women enrolled in the Nurses ' Health Study . METHODS Among 32 826 women who provided a blood specimen , we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection . We assessed iron intake , mutations in the HFE gene that are associated with hereditary hemochromatosis ( i.e. , H63D and C282Y ) , and plasma biochemical measures of total body iron , including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin . Logistic regression models were used to estimate relative risks ( RR ) and 95 % confidence intervals ( CI ) . All statistical tests were two-sided . RESULTS Women with any HFE gene mutation had higher total body iron stores , as reflected by higher transferrin saturations ( P < .001 ) and lower levels of the ratio of transferrin receptors to ferritin ( P = .02 ) , than women with no HFE gene mutation . However , HFE gene mutations were not associated with risk of adenoma ( multivariable RR = 1.08 , 95 % CI = 0.83 to 1.39 ; P = .58 ) . Moreover , comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation ( multivariable RR = 0.96 , 95 % CI = 0.63 to 1.47 ; Ptrend = .66 ) , the ratio of transferrin receptors to ferritin ( multivariable RR = 0.98 , 95 % CI , 0.60 to 1.60 ; Ptrend = .99 ) , or dietary iron intake ( multivariable RR = 1.04 , 95 % CI = 0.68 to 1.57 ; Ptrend = .94 ) . CONCLUSIONS Although our study used several distinct measures of iron status ( i.e. , genetic mutations , biochemical markers , and dietary intake ) and a nested case-control design , we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women A large multicenter r and omized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel , which are precursors of most colorectal malignancies . All subjects ( n = 1905 ; 958 interventions and 947 controls ) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before r and omization . The subjects were followed-up for approximately 4 years after r and omization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after r and omization . Dietary variables were assessed at baseline ( T0 ) and in conjunction with annual visits at the end of the 1st ( T1 ) , 2nd ( T2 ) , 3rd ( T3 ) and 4th ( T4 ) years . Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0 , T1 , T2 , T3 and T4 ( prior to the T4 colonoscopy ) as well as change ( T0–T4 ) in intake . In the intervention group , the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself ( 30 and 31 % for men and women , respectively ) . The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence ( including multiple or advanced adenoma ) , whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence |
430 | 29,435,567 | Pooled effects for anxiety were statistically significant , favoring active treatment .
The analysis found no benefit for insomnia or brain dysfunction and a small beneficial effect for headache . | Cranial electrical stimulation ( CES ) is a noninvasive method of applying low-intensity electrical current to the head .
It is related to but distinct from other forms of transcranial electrical stimulation , including electroconvulsive therapy and transcranial direct current stimulation .
Versions of transcranial electrical stimulation vary in the placement of electrodes and the intensity and waveform of the current ( 1 ) .
According to Guleyupoglu and colleagues ( 1 ) , CES evolved from the concept of electrosleep , first investigated at the beginning of the 20th century .
Most early research and applications occurred in Russia .
Beginning in the 1960s , electrosleep became more popular in the United States .
Because of the belief that the treatment did not actually induce sleep , the name was changed from electrosleep to cranial electrical stimulation ( 1 ) .
Other proposed names , which have not persisted , included transcerebral electrotherapy and NeuroElectric Therapy .
The latter is noteworthy because it gave its name to an early CES device , the Neurotone 101 ( NeuroSystems ) , the first such device approved by the U.S. Food and Drug Administration ( FDA ) ( 1 ) .
The FDA has cleared all subsequent CES devices for marketing on the basis of equivalency to the Neurotone 101 .
Cranial electrical stimulation is among a growing number of noninvasive brain stimulation interventions that change brain function and have been used to treat diseases like depression and anxiety ( 2 ) .
Among the most commonly used CES devices in the United States are the Alpha-Stim products and the Fisher Wallace Stimulator ( Fisher Wallace ) ( 4 ) .
They differ in electrode location ( ear clips in the former and sponge electrodes at the temples in the latter ) and in the amount and type of current .
Both are FDA -cleared for marketing for treatment of anxiety , depression , and insomnia .
Figure 1 shows a typical CES device .
In the United States , CES devices are available only by prescription , although auction Web sites list secondh and devices for sale directly to consumers .
Some countries outside the United States allow consumers to purchase the devices directly from manufacturers .
As a result , physicians may receive requests for prescriptions for CES devices , or their patients may already be using them .
Because of this availability and the exp and ing interest in alternative therapies , we did this systematic review of CES for treating chronic painful conditions , depression , anxiety , and insomnia . | Abstract This double-blind , sham-controlled study sought to investigate the effectiveness of cranial electrotherapy stimulation ( CES ) for the treatment of bipolar II depression ( BD II ) . After r and omization , the active group participants ( n = 7 ) received 2 mA CES treatment for 20 minutes five days a week for 2 weeks , whereas the sham group ( n = 9 ) had the CES device turned on and off . Symptom non-remitters from both groups received an additional 2 weeks of open-label active treatment . Active CES treatment but not sham treatment was associated with a significant decrease in the Beck Depression Inventory ( BDI ) scores from baseline to the second week ( p = 0.003 ) maintaining significance until week 4 ( p = 0.002 ) . There was no difference between the groups in side effects frequency . The results of this small study indicate that CES may be a safe and effective treatment for BD II suggesting that further studies on safety and efficacy of CES may be warranted OBJECTIVES This pilot study examined the potential efficacy of cranial electric stimulation for the treatment of insomnia . DESIGN The research ers tested the hypothesis through a r and omized , double-blind , and placebo controlled clinical trial . The research ers approached eligible subjects who scored 21 or above on the Pittsburgh Insomnia Rating Scale . The research ers then r and omly assigned the subjects to receive either an active or sham device . Each study subject received 60min of active or sham treatment for five days . Following each intervention the subjects completed a sleep log , as well as three and ten days later . SETTING The research ers conducted the study among active duty service members receiving mental health care on the Psychiatry Continuity Service ( PCS ) , Walter Reed National Military Medical Center in Bethesda , MD . MAIN OUTCOME MEASURES The study 's primary outcome variables were the time to sleep onset , total time slept , and number of awakenings as reported by the subjects in the serial sleep logs . The research ers identified a nearly significant increase in total time slept after three cranial electric stimulation treatments among all study subjects . A closer examination of this group revealed an interesting gender bias , with men reporting a robust increase in total time slept after one treatment , decay in effect over the next two interventions , and then an increase in total time slept after the fourth treatment . The research ers speculate that the up and down effect on total time slept could be the result of an insufficient dose of cranial electric stimulation Results of a r and omized , double-blind pilot study indicate that transcranial electrotherapy stimulation may be an effective treatment for the temporary reduction of pain in osteoarthritis patients . Presently , the predominant method for pain management is medication . One very different approach is the application of micro- to milliamp current applied to specific areas of the head , result ing in a release of endogenous opioids from pain management regions of the brain . For the pilot study , 64 subjects suffering from osteoarthritis of the knee and /or hip were enrolled . For two weeks prior , then during and after treatment , subject pain was self-assessed using the visual scale ( VS ) . In addition , subjects were globally assessed by a physician . All subjects , device operators and physicians were blinded as to whether subjects were treated with an active or sham device . Data collected from the study indicate both a decrease in VS pain scores and a significant improvement ( p = 0.05 ) in physician assessment in subjects treated with active devices compared to those treated with the sham device To investigate the effects of microcurrent cranial electrical stimulation ( CES ) therapy on reducing pain and its associated symptoms in fibromyalgia ( FM ) , we conducted a r and omized , controlled , three-group ( active CES device , sham device , and usual care alone [ UC ] ) , double-blind study to determine the potential benefit of CES therapy for symptom management in FM . Those individuals using the active CES device had a greater decrease in average pain ( p = .023 ) , fatigue ( p = .071 ) , and sleep disturbance ( p = .001 ) than individuals using the sham device or those receiving usual care alone over time . Additionally , individuals using the active CES device had improved functional status versus the sham device and UC groups over time ( p = .028 ) Abstract Background Chronic pain is a significant problem for many individuals following spinal cord injury ( SCI ) . Unfortunately , SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments . Cranial electrotherapy stimulation ( CES ) has been effective in managing some types of pain . It involves the application of a small amount of current through the head via ear clip electrodes . Objective Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain . Study design Multi-site , double-blind , sham-controlled study . Participants Adults with SCI and chronic neuropathic pain at or below the level of injury were r and omized to receive active or sham CES . Intervention Application of active CES or sham CES 1 hour daily for 21 days . Six-month open-label phase to assess ‘ as-needed ’ CES use . Outcome measures Change in pre- to post-session pain ratings as well as change in pain intensity , pain interference , pain quality , pain beliefs and coping strategies , general physical and mental health status , depressive symptomatology , perceived stress , and anxiety pre- to post-treatment . Results The active group reported a significantly greater average decrease in pain during daily treatments than the sham group ( Kruskal – Wallis chi-square = 4.70 , P < 0.05 ) . During the 21-day trial , there was a significant group × time interaction for only one outcome variable ; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did ( F = 8.50 , P < 0.01 , d = 0.59 ) . Conclusions On average , CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects . Individual results varied from no pain relief to a great deal of relief Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain . DESIGN A r and omized , double-blind , placebo-controlled trial . SUBJECTS A total of 119 patients with chronic pain . METHODS Patients were treated with either transcranial electrical stimulation or an active placebo device . Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables : visual analogue scale ( pain level ) , SLEEP ( how often does pain disturb sleep ) , FREQ ( frequency of pain ) and MED ( frequency of use of medications to relieve pain ) . RESULTS Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment ( p = 0.0017 between groups ) . Other parameters did not demonstrate significant differences . Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements . CONCLUSION Transcranial electrical stimulation is an effective non-invasive method for pain relief . The active placebo device has a powerful effect on reported pain , which diminishes in the long-term . The involvement of possible neural mechanisms is discussed Objectives . To assess the feasibility of treating musculoskeletal pain in the lower back and /or lower extremities in persons with Parkinson 's disease ( PD ) with cranial electrotherapy stimulation ( CES ) . Design . R and omized , controlled , double-blind trial . Setting . Veterans Affairs Medical Center , Community . Participants . Nineteen persons with PD and pain in the lower back and /or lower extremities . Thirteen provided daily pain rating data . Intervention . Of the thirteen participants who provided daily pain data , 6 were r and omly provided with active CES devices and 7 with sham devices to use at home 40 minutes per day for six weeks . They recorded their pain ratings on a 0-to-10 scale immediately before and after each session . Main Outcome Measure . Average daily change in pain intensity . Results . Persons receiving active CES had , on average , a 1.14-point decrease in pain compared with a 0.23-point decrease for those receiving sham CES ( Wilcoxon Z = −2.20 , P = .028 ) . Conclusion . Use of CES at home by persons with PD is feasible and may be somewhat helpful in decreasing pain . A larger study is needed to determine the characteristics of persons who may experience meaningful pain reduction with CES . Guidelines for future studies are provided Treatments for chronic pain in persons with spinal cord injury ( SCI ) have been less than effective . Cranial electrotherapy stimulation ( CES ) , a noninvasive technique that delivers a microcurrent to the brain via ear clip electrodes , has been shown to effectively treat several neurological and psychiatric disorders . The present study examined the effects of daily 1-hour active CES or sham CES treatment ( r and omly assigned ) for 21 days on pain intensity and interference with activities in 38 males with SCI . The active CES group ( n = 18 ) reported significantly decreased daily pain intensity compared with the sham CES group ( n = 20 ) ( mean change : active CES = -0.73 , sham CES = -0.08 ; p = 0.03 ) . Additionally , the active CES group reported significantly decreased pain interference ( -14.6 pre- vs postintervention , p = 0.004 ) in contrast to the nonsignificant decrease in the sham CES group ( -4.7 pre- vs postintervention , p = 0.24 ) . These results suggest that CES can effectively treat chronic pain in persons with SCI OBJECTIVE To investigate the effects of microcurrent cranial electrical stimulation ( CES ) therapy on activity in pain processing brain regions . DESIGN A r and omized , controlled , three-group , double-blind pilot study . PARTICIPANTS Persons with physician-diagnosed fibromyalgia . INTERVENTION Active CES device , sham device , and usual care alone . RESULTS Those individuals using the active device had a greater decrease in average pain ( P = .023 ) than individuals using the sham device or receiving usual care alone over time . Preliminary analyses of the functional magnetic resonance imaging data on a subset of six participants from each of the two device groups show that individuals using an active CES device had a decrease in activation in the pain processing regions of the brain compared to those using a sham device . CONCLUSIONS The observed decrease in activation in the pain processing regions may indicate a decrease in neural activity in these regions that may be related to decreased pain . This is the first r and omized , controlled trial of CES in patients diagnosed with fibromyalgia to report functional magnetic resonance imaging data We examined efficacy and safety of one specific cranial electrical stimulator ( CES ) device at a fixed setting in subjects with treatment-resistant major depressive disorder ( MDD ) . Thirty subjects ( 57 % female , mean age 48.1 ± 12.3 years ) with MDD and inadequate response to st and ard antidepressants were r and omized to 3 weeks of treatment with CES ( 15/500/15,000 Hz , symmetrical rectangular biphasic current of 1 - 4 mAmp , 40 V ) or sham CES ( device off ) for 20 min , 5 days per week . The primary outcome measure was improvement in the 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) . Adverse effects ( AEs ) were assessed using the Patient Related Inventory of Side Effects ( PRISE ) . Completion rates were 88 % for CES , 100 % for sham . Both treatment groups demonstrated improvement of about 3 - 5 points in HAM-D-17 scores ( p < 0.05 for both ) , and no significant differences were observed between groups . Remission rates were 12 % for CES , and 15 % for sham , a nonsignificant difference . CES was deemed safe , with good tolerability ; poor concentration and malaise were the only distressing AEs that differed significantly between CES and sham ( p = 0.019 and p = 0.043 , respectively ) . Limitations include a small sample and lack of an active comparator therapy . Although both treatment groups improved significantly , this CES at the setting chosen did not separate from sham in this sample . Thus we can not rule out that the benefit from this setting used in this particular form of CES was due to placebo effects . Since this form of CES has other setting s , future studies should test these setting s and compare it against other CES devices . Clinical trials.gov ID : NCT01325532 Since the late 1940s investigators in Russia and Europe have reported that electrosleep therapy is effective for the full spectrum of psychiatric disorders and many “ psychophysiological ” disorders , such as acid-peptic disease , essential hypertension , neurodermatitis etc . Few of these studies are controlled , and to date there is a paucity of double blind , controlled inquiries to aid the clinician in objective evaluation of the indications , contraindications , efficacy , and mode of application for this somatic therapy . A recent controlled study indicates that electrosleep therapy is effective for patients with prominent symptoms of anxiety , insomnia and depression . Our study was design ed to test on a double blind , controlled basis the efficacy of electrosleep therapy on patients with chronic ( more than 2 years ) psychiatric illness unresponsive to current treatment modalities in which the prominent symptoms were anxiety , insomnia , and depression with no evidence of medical illness that could account for these symptoms . All patients received a comprehensive , systematic , diagnostic research interview with diagnoses based on criteria for scoring symptoms positive ( Appendix 1 ) and criteria for each psychiatric syndrome involved ( Appendix 2 ) . Patients were r and omly assigned to one of two groups . Group I patients received 10 active electrosleep treatments followed by 10 sham treatments over a 4-week period . Group II patients received 10 sham electrosleep treatments , followed by 10 active electrosleep treatments over a 4-week period . The Electrosone-50 unit was used and the treatments were identical to those described by Rosenthal and Wulfsohn ( 5 ) . Frequent , double blind , objective and subjective ratings were done to assess clinical improvement . Follow-up ratings were done on a monthly basis for 6 months , except as noted in the paper . Results of the study clearly indicate that active electrosleep treatments have a significant improving effect on sleep , anxiety , and depression , with improvement in psychosocial adjustment . Follow-up data are less impressive . One patient sustained remission ; all other patients who initially responded relapsed during the 1st month . Of these , only 2 responded to a further intensive course of electrosleep therapy , and have subsequently done well with maintenance treatments . Patients diagnosed as having primary depression consistently did worse with active electrosleep treatment . On the basis of our findings , electrosleep therapy appears to have limited value for patients with a chronic psychiatric illness manifested by prominent anxiety , depression , and insomnia . However , some patients may do better with this therapy than with other current treatment modalities . In patients will primary depression , electrosleep therapy should be used with caution , and may be contraindicated . Clearly this is a preliminary study and further systematic clinical and physiological investigation must be done before efficacy and clinical indications are established In cranial electrotherapy stimulation ( CES ) , microcurrent levels of electrical stimulation are passed across the head via electrodes clipped to the ear lobes . After successful clinical use of CES with fibromyalgia patients in our clinic , it was decided to test these results with a double-blind , placebo-controlled study in which 60 r and omly assigned patients were given 3 weeks of 1-hour-daily CES treatments , sham CES treatments , or were held as wait-in-line controls for any placebo effect in the sham-treated patients . Treated patients showed a 28 % improvement in tender point scores , and a 27 % improvement in self-rated scores of general pain level . The number of subjects rating their quality of sleep as poor dropped from 60 % at the beginning of the study to 5 % . In addition , there were significant gains in the self-rated feelings of well-being and quality of life , plus gains in six stress-related psychological test measures . No placebo effect was found among the sham-treated controls . A theoretical role of CES in affecting the brain 's pain message mechanisms and /or neurohormonal control systems is discussed . It is concluded that CES is as effective as the drug therapies in several trials , with no negative side effects , and deserves further consideration as an additional agent for the treatment of fibromyalgia One hundred patients were enrolled in a multicenter double-blind study to evaluate the safety and effectiveness of the Pain Suppressor Unit , a cranial electrotherapy stimulator for the symptomatic treatment of tension headaches . Treatment consisted of extremely low level , high frequency current applied transcranially . Pain scores before and after 20 minute treatments of individual headaches as well as patient and physician global evaluations were the primary efficacy variables . Following use of the active unit , patients reported an average reduction in pain intensity of approximately 35 % . Placebo patients reported a reduction of approximately 18 % . The difference was statistically significant ( p = 0.01 ) . The active unit was rated as moderately or highly effective in 40 % by physicians , and in 36 % by patients . Both physicians and patients scored the placebo unit moderately or highly effective for only 16 % . The difference in ordered outcomes was statistically significant ( p = 0.004 ) . Approximately 10 % of patients in each group reported at least one minor adverse experience . Cranial electrotherapy stimulation is distinct from TENS , and is safe and often effective in ameliorating the pain intensity of tension headaches . It should be considered as an alternative to the chronic usage of analgesics In order to test whether electrosleep is an effective therapeutic procedure , its effects were assessed on the most common of sleep disorders , sleep onset insomnia . The present research was design ed to avoid the inadequacies of previous investigations by a ) using a double blind procedure ; b ) using objective evaluation procedures ( EEG recordings ) ; and c ) using the recommended number and distribution of treatments . Additionally , subjective sleep evaluation and personality-psychopathology data were obtained . Ten volunteers with objective ly established insomnia were r and omly assigned to one of two experimental conditions . These conditions were electrosleep treatment and simulated electrosleep treatment . Initially , each subject ( S ) spend 3 successive nights in the sleep laboratory for the EEG-EOG monitoring of his night-time sleep patterns . This was followed by a series of 24 daytime “ treatments , rdquo ; each 15 minutes in duration . Following this phase , each S again spent 2 nights in the sleep laboratory , at which time post-treatment effects were measured . After 14 no-treatment days , each S returned to the sleep laboratory for follow-up measurement . On the basis of EEG measures , the actual treatment group exhibited a statistically significant decline in the latency of sleep onset , percentage of total bed time awake , and percentage of total sleep time in stage 1 sleep . A significant increase in the percentage of total sleep time in stage 4 and total delta sleep was found . Additionally , subjectively reported latencies of sleep onset declined significantly . These post-treatment results were maintained at follow-up . Significant differences were not found in the simulated treatment group . Possible group differences in age , chronicity of insomnia , psychopathology , sex , participation in psychotherapy , placebo reactivity and suggestibility arc discussed in terms of a “ selective ” placebo effect . These alternatives are discounted before concluding that electrosleep is truly an effective therapeutic procedure in the treatment of sleep onset insomnia BACKGROUND Anxiety disorders are among the most prevalent mental disorders and are usually treated with medication and /or psychotherapy . When anxiety disorders are accompanied with comorbid depression , this further complicates the treatment process . Medication compliance is a common problem due to adverse side effects and new and effective treatments that have minimal side effects are needed for the treatment of anxiety and depression . This study used a r and omized , double-blind , sham controlled design to examine the effectiveness of CES as a treatment for anxiety disorders and comorbid depression in a primary care setting . The study was registered at clinical trials.gov , NCT01533415 . METHODS One hundred and fifteen participants , age 18 years and over , with a primary diagnosis of an anxiety disorder were enrolled from February 2012 to December 2012 The Hamilton Rating Scale for Anxiety ( HAM-A ) and the Hamilton Depression Rating Scale17 ( HAM-D17 ) were used for baseline and outcome measures at weeks one , three , and five . Response to treatment was defined as a reduction of ≥50 % or more on these measures . RESULTS Analysis of covariance revealed a significant difference between the active CES group and the sham CES group on anxiety ( p=0.001 , d=0.94 ) and on depression ( p=0.001 , d=0.78 ) from baseline to endpoint of study in favor of the active CES group . CONCLUSIONS CES significantly decreases anxiety and comorbid depression . Subjects reported no adverse events during the study Gabis L , Shklar B , Geva D : Immediate influence of transcranial electrostimulation on pain and & bgr;-endorphin blood levels : An active placebo-controlled study . Am J Phys Med Rehabil 2003;82:81–85 . Background Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief . Methods We conducted a r and omized , double-blind , placebo-controlled study on 20 chronic back pain patients . They were treated with either transcranial electrostimulation ( TCES ) or an active placebo device . Pain level and serum & bgr;-endorphin levels were measured before and after treatment . Results & bgr;-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group ( P = 0.057 between groups ) . Pain level decreased in eight treated patients and seven control patients ( significant decrease for each group , no significant difference between groups ) . Conclusions Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by & bgr;-endorphin release . The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release . This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on & bgr;-endorphin blood levels The effectiveness and mode of action of electrosleep therapy in chronic hysteria was evaluated in a double blind trial with a 1 month follow-up . Matched groups of hysterics were treated with central electrical stimulation and relaxation , peripheral electrical stimulation and relaxation , or relaxation only . Autogenic training exercises were used initially to st and arize the relaxation instructions for all the patients . Central electrical stimulation has no specific benefit for hysteria . Rhythmic peripheral stimulation does increase the effect of verbal suggestions to relax initially but has no long term advantage over relaxation alone . Regular brief periods of relaxation can improve the mood and diminish the anxiety level of psychiatric out patients with hysteria but have no persistant benefit for sleep disturbance or hypochondriasis . The best treatment of depression in chronic hysterics was found at follow-up to be relaxation without electrostimulation . Specialized somatic and psychotherapeutic methods have no advantage over treatment with low doses of anxiolytic drugs , reassurance , suggestion , and regular periods of relaxation Despite largely negative findings , several subjects reported a remarkable improvement in their symptoms some two to three weeks after electrosleep ( ES ) treatment was concluded , so that it remains unclear whether or not ES may be an effective treatment . The clinical experience reported suggests that five half-hour ES treatments may not be sufficient to produce significant changes in the patient 's anxiety and insomnia . Further investigations are required to examine the effects of varying duration s of treatment Meta-analyses indicate that antidepressants are superior to placebos in statistical terms , but the clinical relevance of the differences has not been established . Previous suggestions of clinical ly relevant effect sizes have not been supported by empirical evidence . In the current paper we apply an empirical method that consists of comparing scores obtained on the Hamilton rating scale for depression ( HAM-D ) and scores from the Clinical Global Impressions-Improvement ( CGI-I ) scale . This method reveals that a HAM-D difference of 3 points is undetectable by clinicians using the CGI-I scale . A difference of 7 points on the HAM-D , or an effect size of 0.875 , is required to correspond to a rating of ' minimal improvement ' on the CGI-I. By these criteria differences between antidepressants and placebo in r and omised controlled trials , including trials conducted with people diagnosed with very severe depression , are not detectable by clinicians and fall far short of levels consistent with clinical ly observable minimal levels of improvement . Clinical significance should be considered alongside statistical significance when making decisions about the approval and use of medications like antidepressants Twenty-eight patients participated in a controlled double-blind study to determine the effectiveness of electrosleep as a treatment modality . To our knowledge this is the first study in the English literature in which the peripheral rhythmic electrical stimulation has been eliminated , thereby allowing the results of the current effect on the brain to be independently evaluated . Both global ratings by patients and physicians on the fifth day of treatment and on two-week follow-up indicate that current effect is not associated with significant improvement , although patient global ratings on day 5 indicate a trend in this direction . Self-rating scales by patients indicate no significant improvement for anxiety , insomnia , or somatic complaints . Depressive self-rating scales do show a significant improvement on day 5 of treatment , but no carry over effect to the two-week follow-up Ten subjects who had suffered from sleep onset insomnia for a minimun of 2 years participated in a double blind study of the effects of electrosleep on this disorder . This paper reports a 2-year follow-up of these subjects . Of the five subjects who received 24 live treatments , four appeared to be able to fall asleep with little difficulty and to awake feeling moderately to very well rested . Only one appeared to have relapsed during the 2-year-no-treatment period . Of those receiving sham treatment four were having quite a bit of difficulty falling asleep but three of the five awoke feeling moderately well rested . Although the number of subjects is small , the trends appear consistent with the interpretation that sleep habits were improved for most of the real treatment subjects and for few of those receiving sham treatment |
431 | 28,320,733 | There is limited evidence of mental health and cognitive differences in some individuals with PFP .
Features demonstrating linear correlations with pain and physical function included anxiety/depression , catastrophising , praying and hoping and pain-related fear .
Conclusions Anxiety , depression , catastrophising and fear of movement may be elevated in individuals with PFP and correlate with pain and reduced physical function . | Background Patellofemoral pain ( PFP ) is prevalent in adolescence and adulthood and often persists .
In contrast to other persistent musculoskeletal conditions , for which non-physical , psychological features are implicated , PFP remains largely conceptualised in mechanical terms .
Aims To ( 1 ) identify whether the psychological characteristics of individuals with PFP differs from asymptomatic controls and ( 2 ) evaluate the correlations between psychological characteristics and PFP severity . | Background One of the rationale s behind using strength training in the treatment of adolescents with Patellofemoral Pain ( PFP ) is that reduced strength of the lower extremity is a risk factor for PFP and a common deficit . This rationale is based on research conducted on adolescents > 15 years of age but has never been investigated among young adolescents with PFP . Objectives To compare isometric muscle strength of the lower extremity among adolescents with PFP compared to age- and gender-matched pain-free adolescents . Methods In 2011 a population -based cohort ( APA2011-cohort ) consisting of 768 adolescents aged 12–15 years from 8 local schools was formed . In September 2012 , all adolescents who reported knee pain in September 2011 were offered a clinical examination if they still had knee pain . From these , 20 adolescents ( 16 females ) were diagnosed with PFP . Pain-free adolescents from the APA2011-cohort ( n = 20 ) were recruited on r and om basis as age- and gender-matched pairs . Primary outcome was isometric knee extension strength normalized to body weight ( % BW ) and blinded towards subject information . Secondary outcomes included knee flexion , hip abduction/adduction and hip internal/external rotation strength . Demographic data included Knee Injury and Osteoarthritis Outcome Score ( KOOS ) and symptom duration . Results Adolescents with PFP reported long symptom duration and significantly worse KOOS scores compared to pain-free adolescents . There were no significant differences in isometric knee extension strength ( Δ0.3 % BW , p = 0.97 ) , isometric knee flexion strength ( Δ0.4 % BW , p = 0.84 ) or different measures of hip strength ( Δ0.4 to 1.1 % BW , p>0.35 ) . Conclusion Young symptomatic adolescents with PFP between 12 and 16 years of age did not have decreased isometric muscle strength of the knee and hip . These results question the rationale of targeting strength deficits in the treatment of adolescents with PFP . However , strength training may still be an effective treatment for those individuals with PFP suffering from strength deficits Objectives Describe proportions of individuals with patellofemoral pain ( PFP ) with an unfavourable recovery over 12 months ; identify clinical predictors of poor recovery at 3 and 12 months ; and determine baseline values of predictors that identify those with poor 12-month prognosis . Methods An observational analysis utilised data from 310 individuals with PFP enrolled in two r and omised clinical trials . Thirteen baseline variables ( participant , PFP , study characteristics ) were investigated for their prognostic ability . Pain , function and global recovery were measured at 3 and 12 months . Multivariate backward stepwise regression analyses ( treatment-adjusted , p<0.10 ) were performed for each follow-up measure . Receiver operator characteristic curves identified cut-points associated with unfavourable recovery at 12 months . Results 55 % and 40 % of participants had an unfavourable recovery at 3 and 12 months , respectively . Longer baseline pain duration was significantly associated with poor 3-month and 12-month recovery on measures of pain severity ( β 11.36 to 24.94 ) , Anterior Knee Pain ( AKP ) Scale ( −4.44 to −11.33 ) and global recovery ( OR : 2.32 to 6.11 ) . Greater baseline pain severity and lower AKP Scale score were significantly associated with poor recovery on multiple measures ( p<0.05 ) . Baseline duration > 2 months and AKP Scale score < 70/100 were associated with unfavourable 12-month recovery . Conclusions A substantial number of individuals with PFP have an unfavourable recovery over 12 months , irrespective of intervention . Knee pain duration > 2 months is the most consistent prognostic indicator , followed by AKP Scale score < 70 . Sports medicine practitioners should utilise interventions with known efficacy in reducing PFP , and promote early intervention to maximise prognosis . Trial registration Australian study : Australian Clinical Trials Registry ( ACTRN012605000463673 ) , Clinical Trials.gov ( NCT00118521 ) ; Dutch study : International St and ard R and omised Controlled Trial Number Register ( IS RCT N83938749 Purpose The purpose of the study was to investigate if changes in psychological variables are related to the outcome in pain and disability in patients with chronic anterior knee pain . Methods A longitudinal observational study on 47 patients with chronic anterior knee pain was performed in a secondary healthcare setting . Pain was measured with the visual analogue scale and disability with the Lysholm scale . The psychological variables , such as anxiety , depression , pain coping strategies , catastrophizing and fear to movement beliefs , were studied by using self-administered question naires . Results Among the pain coping strategies , only the catastrophizing subscale showed a significant reduction . Similarly , anxiety , depression and kinesiophobia were significantly reduced after treatment . Those patients who decreased the catastrophizing , kinesiophobia , anxiety and depression showed a greater improvement in pain and disability after a purely biomedical treatment . A multiple regression analysis revealed that changes in catastrophizing predicted the amount of improvement in pain severity and that changes in both catastrophizing and anxiety predicted changes in disability after treatment . Conclusion What has been found suggests that clinical improvement in pain and disability is associated with a reduction in catastrophizing and kinesiophobia . Therefore , co- interventions to reduce catastrophizing thinking and kinesiophobia may enhance the results .Level of evidence Prospect i ve Cohort Study , Level I for prognosis AIM To study the prevalence of persistent post-surgical pain ( PPSP ) and neuropathic pain ( NP ) after total knee replacement ( TKR ) . METHODS MEDLINE and Embase data bases were search ed for articles published until December 2014 in English language . Published articles were included if they referred to pain that lasts at least 3 mo after primary TKR for knee osteoarthritis , and measured pain with pain specific instruments . Studies that referred to pain caused by septic reasons and implant malalignment were excluded . Both prospect i ve and retrospective studies were included and only 14 studies that match the inclusion criteria were selected for this review . RESULTS The included studies were characterized by the heterogeneity on the scales used to measure pain and pre-operative factors related to PPSP and NP . The reported prevalence of PPSP and NP seems to be relatively high , but it varies among different studies . There is also evidence that the prevalence of post-surgical pain is related to the scale used for pain measurement . The prevalence of PPSP is ranging at 6 mo from 16 % to 39 % and at 12 mo from 13.1 % to 23 % and even 38 % of the patients . The prevalence of NP at 6 mo post-operatively is ranging from 5.2 % to 13 % . Pre-operative factors related to the development of PPSP also differ , including emotional functioning , such as depression and pain catastrophizing , number of comorbidities , pain problems elsewhere and operations in knees with early grade of osteoarthritis . CONCLUSION No firm conclusions can be reached regarding the prevalence of PPSP and NP and the related factors due to the heterogeneity of the studies & NA ; Few studies have investigated whether prognostic indicators , which contribute to the transition from acute to chronic low back pain ( LBP ) , are also those which contribute to continuing persistence of chronic LBP . We compared the contribution of physical , psychological and social indicators to predicting disability after one year between consulters with LBP of less than 3 months duration and more than 3 months duration . Data from two large prospect i ve cohort studies of consecutive patients consulting with LBP in general practice s were merged , providing complete data for 258 cases with acute/subacute LBP and 668 cases with chronic LBP at 12 months follow‐up . There were significant differences between the two LBP groups in baseline characteristics and clinical course of disability , assessed by Rol and Morris Disability Question naire , during the year of follow‐up . Adjusted associations between potential prognostic indicators and disability at 12 months were carried out in the two LBP subgroups . The final multivariable regression models showed that being non‐employed , having widespread pain , a high level of Chronic Pain Grade , and catastrophising were the strongest prognostic indicators for disability at 12 months in both LBP groups . Fear of pain was significantly associated with disability in chronic LBP . Importantly , beyond baseline disability , the effect size of the other prognostic indicators for poor outcome was rather low . These findings must continue to challenge research ers to identify useful early predictors of outcome in persons with disabling back pain , as screening and targeted treatment approaches are dependent upon prognostic indicators with clinical significance & NA ; The objective of this study is to determine whether depression is an independent risk factor for onset of an episode of troublesome neck and low back pain . There is growing evidence that pain problems increase the risk of depression . However , the evidence about the role of depression as a risk factor for onset of pain problems is contradictory . This lack of consistency in research findings may be due in part to method ological weaknesses in existing studies , for example , use of an inappropriate study design and inadequate consideration of confounding . A population ‐based r and om sample of adults was surveyed and followed at 6 and 12 months . Individuals at risk of troublesome ( intense and /or disabling ) neck or low back pain are the subjects of this report ( n=790 ) . We used Cox proportional hazards models to measure the time‐varying effect of depressive symptoms on the onset of troublesome neck and low back pain . Our multivariable analysis considered the possible confounding effects of demographic and socio‐economic factors , health status , co‐morbid medical conditions and injuries to the neck or low back . We found an independent and robust relationship between depressive symptoms and onset of an episode of pain . In comparison with the lowest quartile of scores ( the least depressed ) , those in the highest quartile of depression scores had a four‐fold increased risk of troublesome neck and low back pain ( adjusted HRR 3.97 ; 95 % CI 1.81–8.72 ) . Depression is a strong and independent predictor for the onset of an episode of intense and /or disabling neck and low back pain Purpose This r and omized controlled trial had two main aims . The first aim was to investigate the effect of early preventive , psychologically informed , interventions for pain-related disability . The second aim was explore whether people who are matched to an intervention specifically targeting their psychological risk profile had better outcomes than people who were not matched to interventions . Methods A total of 105 participants were recruited from their workplace , screened for psychological risk factors and classified as being at risk for long-term pain-related disability . They were subgrouped into one of three groups based on their psychological profile . Three behaviorally oriented psychological interventions were developed to target each of the three risk profiles . Half of the participants were assigned a matched intervention developed to target their specific profile , and half were assigned an unmatched intervention . After treatment , repeated measure ANOVAs and χ2 tests were used to determine if treatments had an effect on primary and secondary outcomes including perceived disability , sick leave , fear and avoidance , pain catastrophizing and distress , and if matched participants had better outcomes than did unmatched . Results Treatments had effects on all outcome variables ( effect sizes d ranging between 0.23 and 0.66 ) , but matched participants did not have better outcomes than unmatched . Conclusions Early , preventive interventions have an impact on a number of outcome variables but it is difficult to realize a matching procedure . More in-depth research of the process of matching is needed This study was a prospect i ve single blind r and omised controlled trial to compare the effects of rehabilitation with emphasis on retraining the vastus medialis ( VMO ) component of the quadriceps femoris muscle and rehabilitation with emphasis on general strengthening of the quadriceps femoris muscles on pain , function and Quality of Life in patients with patellofemoral pain syndrome ( PFPS ) . Patients with PFPS ( n=69 ) were recruited from a hospital orthopaedic clinic and r and omised into three groups : ( 1 ) physiotherapy with emphasis on selectively retraining the VMO ( Selective ) ; ( 2 ) physiotherapy with emphasis on general strengthening of the quadriceps femoris muscles ( General ) ; and ( 3 ) a no-treatment control group ( Control ) . The three groups were then compared before and after an eight-week rehabilitation period . The Selective and General groups demonstrated statistically significant and ' moderate ' to ' large ' effect size reductions in pain when compared to the Control group . Both the Selective and General groups displayed statistically significant and ' moderate ' and ' large ' effect size improvements in subjective function and Quality of Life compared to the Control group . Knee flexion excursion during the stance phase of gait , demonstrated that there were no statistical significant differences and only ' trivial ' to ' small ' effect size differences between the Selective or General groups and the Control group . A large number of PFPS patients can experience significant improvements in pain , function and Quality of Life , at least in the short term , with quadriceps femoris rehabilitation , with or without emphasis on selective activation of the VMO component . Both approaches would seem acceptable for rehabilitating patients with PFPS . It may be appropriate to undertake exercises involving selective activation of the vastus medialis early in the rehabilitation process , however , clinicians should not overly focus on selective activation before progressing rehabilitation , especially in more chronic cases with significant participation restrictions Background Patellofemoral pain ( PFP ) has traditionally been viewed as self-limiting , but recent studies show that a large proportion of patients report chronic knee pain at long-term follow-up . We identified those patients with an unfavourable recovery ( ‘ moderate improvement ’ to ‘ worse than ever ’ measured on a Likert scale ) and examined whether there is an association between PFP and osteoarthritis ( OA ) at 5–8-year follow-up . Methods Long-term follow-up data were derived from 2 r and omised controlled trials ( n=179 , n=131 ) . Patient-reported measures were obtained at baseline . Pain severity ( 100 mm visual analogue scale ( VAS ) ) , function ( Anterior Knee Pain Scale ( AKPS ) ) and self-reported recovery were measured 5–8 years later , along with knee radiographs . Multivariate backward stepwise linear regression analyses were used to evaluate the prognostic ability of baseline pain duration , pain VAS and AKPS on outcomes of pain VAS and AKPS at 5–8 years . Results 60 ( 19.3 % ) participants completed the question naires at 5–8-year follow-up ( 45 women , mean age at baseline 26 years ) and 50 underwent knee radiographs . No differences were observed between responders and non-responders regarding baseline demographics , and 3-month and 12-month pain severity and recovery . 34 ( 57 % ) reported unfavourable recovery at 5–8 years . 48 out of 50 participants ( 98 % ) had no signs of radiographic knee OA . Multivariate models revealed that baseline PFP duration ( > 12 months ; R2=0.22 ) and lower AKPS ( R2=0.196 ) were significant predictors of poor prognosis at 5–8 years on measures of worst pain VAS and AKPS , respectively . Summary and conclusion More than half of participants with PFP reported an unfavourable recovery 5–8 years after recruitment , but did not have radiographic knee OA . Longer PFP duration and worse AKPS score at baseline predict poor PFP prognosis . Education of health practitioners and the general public will provide patients with more realistic expectations regarding prognosis Many variables have retrospectively been associated with the presence of anterior knee pain . Very few prospect i ve data exist , however , to determine which of these variables will lead to the development of anterior knee pain . It was our purpose in this study to determine the intrinsic risk factors for the development of anterior knee pain in an athletic population over a 2-year period . Before the start of training , 282 male and female students enrolled in physical education classes were evaluated for anthropometric variables , motor performance , general joint laxity , lower leg alignment characteristics , muscle length and strength , static and dynamic patellofemoral characteristics , and psychological parameters . During this 2-year follow-up study , 24 of the 282 students developed patellofemoral pain . Statistical analyses revealed a significant difference between those subjects who developed patellofemoral pain and those who did not concerning quadriceps and gastrocnemius muscle flexibility , explosive strength , thumb-forearm mobility , reflex response time of the vastus medialis obliquus and vastus lateralis muscles , and the psychological parameter of seeking social support . However , only a shortened quadriceps muscle , an altered vastus medialis obliquus muscle reflex response time , a decreased explosive strength , and a hypermobile patella had a significant correlation with the incidence of patellofemoral pain . We concluded that the latter four parameters play a dominant role in the genesis of anterior knee pain and we therefore deem them to be risk factors for this syndrome The objective of this paper was to determine the cost effectiveness of exercise therapy ( intervention group ) compared with " usual care " ( control group ) in adolescents and young adults with the patellofemoral pain syndrome in primary care . This multicenter prospect i ve r and omized clinical trial with cost-utility analysis was conducted at 38 general practice s and three sport medical advice centers in the Netherl and s for 2007 . A total of 131 patients were included . The annual direct medical costs per patient were significantly higher for the intervention group ( euro 434 ) compared with the control group ( euro 299 ) mainly caused by additional physiotherapy visits . The average annual societal costs per patient were significantly lower in the intervention group ( euro 1011 vs euro 1.166 ) . Productivity costs were the largest cost component , in particular costs due to reduced efficiency at paid work which were responsible for 47 % and 56 % of the total costs in the intervention and control group respectively . Patients in the intervention group experienced a slightly , but not significantly , higher quality of life ( 0.8722 vs 0.8617 ) . With a cost effectiveness ratio of -euro 14,738 per quality adjusted life year , exercise therapy appears to be cost effective as compared with " usual care . PURPOSE Gait metric alterations have been previously reported in patients suffering from anterior knee pain ( AKP ) . Characterization of simple and measureable gait parameters in these patients may be valuable for assessing disease severity as well as for follow-up . Previous gait studies in this population have been comprised of relatively small cohorts and the findings of these studies are not uniform . The objective of the present study was to examine spatio-temporal gait parameters in patients with AKP in comparison to symptom-free controls . Furthermore , the study aim ed to examine the relationship between self-reported disease severity and the magnitude of gait abnormalities . METHODS 157 patients with AKP were identified and compared to 31 healthy controls . Patients were evaluated with a spatiotemporal gait analysis via a computerized mat , the Western Ontario and McMaster Osteoarthritis Index ( WOMAC ) question naire and the Short Form (SF)-36 health surveys . RESULTS AKP patients walked with significantly lower velocity ( 15.9 % ) and cadence ( 5.9 % ) , shorter step length ( 9.5 % ) , stride length ( 9.6 % ) , and showed significant differences in all gait cycle phases ( P<0.05 for all ) . Study group reported higher levels of pain ( 96 % ) , functional limitation ( 94 % ) , and poorer perception of mental quality of life ( 30 % ) ( P<0.05 for all ) . CONCLUSION Significant differences were found between the spatiotemporal gait profile of AKP patients and symptom-free matched controls . In addition , an association was found between subjective disease severity and gait abnormalities . These findings suggest the usefulness of gait parameters , alongside with the use of self-evaluation question naires , in identifying deviations of these patients from healthy population BACKGROUND Treatment of patellofemoral pain syndrome ( PFPS ) has been extensively studied in physical therapy literature . Patients with PFPS demonstrate quadriceps and hip musculature weakness , altered lower extremity ( LE ) kinematics , and decreased LE flexibility . Psychosocial factors have also been identified as an important factor in patients with PFPS . The authors hypothesize that an ordered approach addressing each of these impairments sequentially will result in greater improvement in PFPS symptoms . The purpose of this pilot study was to assess the feasibility of performing a r and omized trial and to determine the sample size necessary to examine the validity of this hypothesis . METHODS Patients received a sequential treatment approach using a PFPS treatment algorithm ( PFPS Algorithm ) design ed by the authors . Patients were evaluated assessing psychosocial factors , flexibility , LE kinematics , and LE strength . Impairments that were found in the evaluation were addressed sequentially over the episode of care . Patients were prescribed therapy two times per week for six weeks . Pain , Anterior Knee Pain Scale ( AKPS ) , and Global Rating of Change ( GROC ) were measured at evaluation and discharge . RESULTS Thirty consecutive patients with PFPS who were referred to physical therapy were enrolled in the pilot study . All phases of the feasibility study including recruitment , treatment protocol s and data collection were effectively carried out . One hundred percent of patients treated with the PFPS algorithm who completed the prescribed treatment had a clinical ly significant improvement in the AKPS and GROC . A floor effect was noted with NPRS with 38 % of patients unable to achieve clinical ly significant improvement . CONCLUSIONS With minor changes to the protocol and outcome measures used , a full r and omized trial is feasible and merited . Steps must be taken to reduce the high drop-out rate among both groups . LEVEL OF EVIDENCE 1b There is growing evidence for the idea that in back pain patients , pain-related fear ( fear of pain/physical activity/(re)injury ) may be more disabling than pain itself . A number of question naires have been developed to quantify pain-related fears , including the Fear-Avoidance Beliefs Question naire ( FABQ ) , the Tampa Scale for Kinesiophobia ( TSK ) , and the Pain Anxiety Symptoms Scale ( PASS ) . A total of 104 patients , presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aim ed at ( 1 ) replicating that pain-related fear is more disabling than pain itself ( 2 ) investigating the association between pain-related fear and poor behavioral performance and ( 3 ) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs ( e.g. pain catastrophizing ) . All three studies showed similar results . Highest correlations were found among the pain-related fear measures and measures of self-reported disability and behavioral performance . Even when controlling for sociodemographics , multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance . The PASS appeared more strongly associated with pain catastrophizing and negative affect , and was less predictive of pain disability and behavioral performance . Implication s for chronic back pain assessment , prevention and treatment are discussed Background Patellofemoral pain ( PFP ) is common among adolescents and associated with long-lasting pain and disability . Patient education and exercise therapy are commonly used treatments in primary and secondary care but the effect of these treatments in adolescents is unknown . We aim ed to determine the effect of exercise therapy as an add-on therapy to patient education compared with education alone . Methods 121 adolescents from 15–19 years of age were cluster r and omised to patient education or patient education combined with exercise therapy . Patient education covered self-management of pain and information on PFP . Exercise therapy consisted of supervised exercises on school premises ( 3/week for 3 months ) and instructions on home-based exercises . Adherence to exercises was assessed as attendance and weekly text messages . Primary outcome measure was self-reported recovery ( seven-point Likert scale ) at 12 months with additional follow-ups at 3 , 6 and 24 months . Results Adolescents r and omised to patient education and exercise therapy were more likely to have recovered at 12 months ( OR , 1.73 , 95 % CI 1.02 to 2.93 , number needed to treat ( NNT ) of 11 ) . Similar results were observed at 3 and 6 months ( OR 1.88 and 1.43 ) while the effect was further increased at 24 months ( OR of 2.52 , NNT of 5 ) . A higher total number of weekly exercise sessions increased the odds of recovery . Conclusions In adolescent PFP , the addition of exercise therapy for 3 months was more effective than patient education alone . The effect was apparent at 3 months and increased up to 2 years . Adherence to exercises was important and improved the odds of recovery . Trial registration number clinical trials.gov reference : NCT01438762 Study Design . Prospect i ve cohort study with patients with chronic low back pain ( CLBP ) at primary care setting . Objective . The aim of our study was to identify predictors for transition from localized CLBP to chronic widespread pain in general practice . In contrast to the typically investigated risk factors , this study also focuses intensively on protective factors , which decrease the probability of chronic widespread pain . For this , we investigated the re sources resilience and coping strategies , which are suspected as potential protective factors for incident chronic pain syndromes . Summary of Background Data . In primary care , about a quarter of patients with CLBP experience chronic widespread pain ( CWP ) . Methods . Patients experiencing localized CLBP were included and evaluated after a 6- and 12-month follow-up period regarding the development of CWP . Potential risk factors ( sociodemographic data , pain characteristics , depression , anxiety , somatization ) , protective factors ( resilience , coping strategies ) , and sample characteristics were assessed at baseline . Predictor identification was done by multivariate logistic regression analysis . Results . The 1-year incidence for the onset of CWP among patients with CLBP was 23.8 % . We identified the 3 risk factors , female sex , long duration of back pain , and a high rate of psychosomatic symptoms , for the onset of CWP among patients with CLBP . Coping re sources and resilience had no impact on the transition from CLBP to CWP . Conclusion . The results suggest that CWP is no independent entity but rather a particularly negative occurrence on a continuum of chronic pain . Processes of somatization play a major role in the development of this extreme . Level of Evidence : Background The effectiveness of risk stratification for low back pain ( LBP ) management has not been demonstrated in outpatient physical therapy setting s. Objective The purpose s of this study were : ( 1 ) to assess implementation of a stratified care approach for LBP management by evaluating short-term treatment effects and ( 2 ) to determine feasibility of conducting a larger-scale study . Design This was a 2-phase , preliminary study . Methods In phase 1 , clinicians were r and omly assigned to receive st and ard ( n=6 ) or stratified care ( n=6 ) training . Stratified care training included 8 hours of content focusing on psychologically informed practice . Changes in LBP attitudes and beliefs were assessed using the Pain Attitudes and Beliefs Scale for Physiotherapists ( PABS-PT ) and the Health Care Providers Pain and Impairment Relationship Scale ( HC-PAIRS ) . In phase 2 , clinicians receiving the stratified care training were instructed to incorporate those strategies in their practice and 4-week patient outcomes were collected using a numerical pain rating scale ( NPRS ) , and the Oswestry Disability Index ( ODI ) . Study feasibility was assessed to identify potential barriers for completion of a larger-scale study . Results In phase 1 , minimal changes were observed for PABS-PT and HC-PAIRS scores for st and ard care clinicians ( Cohen d=0.00–0.28 ) . Decreased biomedical ( −4.5±2.5 points , d=1.08 ) and increased biopsychosocial ( + 5.5±2.0 points , d=2.86 ) treatment orientations were observed for stratified care clinicians , with these changes sustained 6 months later on the PABS-PT . In phase 2 , patients receiving stratified care ( n=67 ) had greater between-group improvements in NPRS ( 0.8 points ; 95 % confidence interval=0.1 , 1.5 ; d=0.40 ) and ODI ( 8.9 % points ; 95 % confidence interval=4.1 , 13.6 ; d=0.76 ) scores compared with patients receiving st and ard physical therapy care ( n=33 ) . Limitations In phase 2 , treatment was not r and omly assigned , and therapist adherence to treatment recommendations was not monitored . This study was not adequately powered to conduct subgroup analyses . Conclusions In physical therapy setting s , biomedical orientation can be modified , and risk-stratified care for LBP can be effectively implemented . Findings from this study can be used for planning of larger studies |
432 | 22,700,393 | Studies by radiology authors showed a trend towards stronger preference for CTC compared with studies by gastroenterology authors .
Symptomatic patients expressed no preference , but screening patients preferred CTC .
There was no difference in preferences between studies using “ masked ” and “ unmasked ” preference ascertainment methods .
There was no evidence of publication bias , while cumulative and exclusion analysis did not show any temporal trend or dominant study .
In conclusion , most included studies reported preference for CTC .
On stratified analysis , screening patients preferred CTC while diagnostic patients showed no preference .
Studies published in radiology journals showed significantly stronger preference for CTC compared with studies in gastroenterology or general medicine journals | In recent years , colorectal cancer ( CRC ) screening using computerized tomographic colonography ( CTC ) has attracted considerable attention .
In order to better underst and patient preferences for CTC versus colonoscopy , we performed a systematic review and meta- analysis of the available literature . | The purpose of this study was to prospect ively compare participant experience and preference of limited preparation computed tomography colonography ( CTC ) with full-preparation colonoscopy in a consecutive series of patients at increased risk of colorectal cancer . CTC preparation comprised 180 ml diatrizoate meglumine , 80 ml barium and 30 mg bisacodyl . For the colonoscopy preparation 4 l of polyethylene glycol solution was used . Participants ’ experience and preference were compared using the Wilcoxon signed rank test and the chi-squared test , respectively . Associations between preference and experience parameters for the 173 participants were determined by logistic regression . Diarrhoea occurred in 94 % of participants during CTC preparation . This side effect was perceived as severely or extremely burdensome by 29 % . Nonetheless , the total burden was significantly lower for the CTC preparation than for colonoscopy ( 9 % rated the CTC preparation as severely or extremely burdensome compared with 59 % for colonoscopy ; p < 0.001 ) . Participants experienced significantly more pain , discomfort and total burden with the colonoscopy procedure than with CTC ( p < 0.001 ) . After 5 weeks , 69 % preferred CTC , 8 % were indifferent and 23 % preferred colonoscopy ( p < 0.001 ) . A burdensome colonoscopy preparation and pain at colonoscopy were associated with CTC preference ( p < 0.04 ) . In conclusion , participants ’ experience and preference were rated in favour of CTC with limited bowel preparation compared with full-preparation colonoscopy CONTEXT Conventional colonoscopy is the best available method for detection of colorectal cancer ; however , it is invasive and not without risk . Computed tomographic colonography ( CTC ) , also known as virtual colonoscopy , has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers . OBJECTIVE To assess the accuracy of CTC in a large number of participants across multiple centers . DESIGN , SETTING , AND PARTICIPANTS A nonr and omized , evaluator-blinded , noninferiority study design of 615 participants aged 50 years or older who were referred for routine , clinical ly indicated colonoscopy in 9 major hospital centers between April 17 , 2000 , and October 3 , 2001 . The CTC was performed by using multislice scanners immediately before st and ard colonoscopy ; findings at colonoscopy were reported before and after segmental unblinding to the CTC results . MAIN OUTCOME MEASURES The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm . Secondary outcomes included detection of all lesions , detection of advanced lesions , possible technical confounders , participant preferences , and evidence for increasing accuracy with experience . RESULTS A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures ; 104 participants had lesions sized at least 6 mm . The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0 % ( 95 % confidence interval [ CI ] , 29.6%-48.4 % ) and for lesions sized at least 10 mm , it was 55.0 % ( 95 % CI , 39.9%-70.0 % ) . These results were significantly lower than those for conventional colonoscopy , with sensitivities of 99.0 % ( 95 % CI , 97.1%->99.9 % ) and 100 % , respectively . A total of 496 participants were without any lesion sized at least 6 mm . The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5 % ( 95 % CI , 87.9%-93.1 % ) and 100 % , respectively , and without lesions sized at least 10 mm , 96.0 % ( 95 % CI , 94.3%-97.6 % ) and 100 % , respectively . Computed tomographic colonography missed 2 of 8 cancers . The accuracy of CTC varied considerably between centers and did not improve as the study progressed . Participants expressed no clear preference for either technique . CONCLUSIONS Computed tomographic colonography by these methods is not yet ready for widespread clinical application . Techniques and training need to be improved PURPOSE To compare reduced colonic cleansing based on dietary fecal tagging ( FT ) with st and ard ( non-FT ) colonic cleansing with regard to patient acceptance , sensitivity , and specificity . MATERIAL S AND METHODS In 50 patients ( FT group ) , FT was performed by means of diet , magnesium citrate , and a barium suspension . In another 50 patients ( non-FT group ) , preparation was based on polyethylene glycol administration . All patients underwent conventional colonoscopy after computed tomographic ( CT ) colonography . Sensitivity and specificity for polyp detection were calculated by using conventional colonography as the reference st and ard . At CT colonography , fecal residue was evaluated . Patients were interviewed to determine discomfort , side effects , sleep quality , final opinion on examination comfort , and whether they would be reluctant to undergo the same examination again . RESULTS FT left more fecal residue but improved differentiation from polyps ( FT specificity , 88 % [ 30 of 34 patients ] ; non-FT , 77 % [ 23 of 30 patients ] ) . Sensitivities were comparable : FT , 88 % ( 14 of 16 patients ) ; non-FT , 85 % ( 17 of 20 patients ) . FT significantly reduced discomfort , side effects , and sleep disturbance , and result ed in an improved final opinion of how comfortable the examination was ( P < .05 ) . Although FT improved patient willingness to repeat the examination , this improvement was not statistically significant ( P > .05 ) . CONCLUSION FT offers the patient a well-tolerated preparation and improves specificity , with improved differentiation of polyps from residual stool BACKGROUND AND AIMS We prospect ively compared the performance of low-dose multidetector computed tomographic colonography ( CTC ) without cathartic preparation with that of colonoscopy for the detection of colorectal polyps . METHODS A total of 203 patients underwent low-dose CTC without cathartic preparation followed by colonoscopy . Before CTC , fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals . No subtraction of tagged feces was performed . Colonoscopy was performed 3 - 7 days after CTC . Three readers interpreted the CTC examinations separately and independently using a primary 2-dimensional approach using multiplanar reconstructions and 3-dimensional images for further characterization . Colonoscopy with segmental unblinding was used as reference st and ard . The sensitivity of CTC was calculated both on a per-polyp and a per-patient basis . For the latter , specificity , positive predictive values , and negative predictive values were also calculated . RESULTS CTC had an average sensitivity of 95.5 % ( 95 % confidence interval [ CI ] , 92.1%-99 % ) for the identification of colorectal polyps > or = 8 mm . With regard to per-patient analysis , CTC yielded an average sensitivity of 89.9 % ( 95 % CI , 86%-93.7 % ) , an average specificity of 92.2 % ( 95 % CI , 89.5%-94.9 % ) , an average positive predictive value of 88 % ( 95 % CI , 83.3%-91.5 % ) , and an average negative predictive value of 93.5 % ( 95 % CI , 90.9%-96 % ) . Interobserver agreement was high on a per-polyp basis ( kappa statistic range , .61-.74 ) and high to excellent on a per-patient basis ( kappa statistic range , .79-.91 ) . CONCLUSIONS Low-dose multidetector CTC without cathartic preparation compares favorably with colonoscopy for the detection of colorectal polyps BACKGROUND As part of a multicenter , r and omized controlled trial of the efficacy of flexible sigmoidoscopy for the prevention of bowel cancer , an investigation of the predictors of screening interest was carried out in a sub sample of older adults . METHOD The aim of the study was to establish the predictive power of the Health Belief Model ( HBM ) and to evaluate the contribution of HBM elements in mediating the effect of other demographic and health variables which have been found to be associated with screening interest and participation . A total of 5,099 participants were sent a postal question naire which examined screening interest , attitudes toward screen ing ( benefits and barriers ) , perceived bowel cancer risk , bowel cancer worry , bowel symptoms , health status , state anxiety , and optimism . A total of 3,648 question naires were returned completed , giving a response rate of 71.5 % . RESULTS The results showed that threat , barriers , and benefits explained 47 % of the variance in interest . Demographic and health variables were also associated with screening interest , although most of their effect was mediated by the HBM constructs . DISCUSSION This community study in older adults showed a high level of interest in participating in screening . The large sample size provided the opportunity to test the value of the HBM model and to examine mediation of demographic and health variables . The HBM proved to be a good model of screening interest . These results further our underst and ing of the decision processes in participating in cancer screening and point to directions to increase the level of participation in community sample BACKGROUND Response rates , patient sample characteristics , and patient satisfaction ratings were compared between two surveying methods : ( 1 ) surveys completed at the physician office site ( on-site surveying ) , and ( 2 ) surveys mailed to patient homes following the encounter ( mail-out/mail-back ) . METHODS Surveying was completed at three physician practice s within a 214-physician medical practice . Patients with physician appointments during four-hour time blocks were r and omly split to receive either on-site or mail-based satisfaction surveys . RESULTS Participants younger than 45 years of age provided much higher satisfaction ratings on site than they did by mail ( p < .0001 ) , and participants older than 45 years of age reported satisfaction levels consistently whether on site or by mail . Both age groups reported higher satisfaction with " people aspects " of care on site than they did by mail ( p < .001 ) . DISCUSSION On-site methods may yield satisfaction results that are biased in a positive direction for younger patients and for all patients in which social desirability pressures are prominent . Therefore , organizations that rely on such information may have an inflated view of the patient 's satisfaction with their care delivery experience . Secondly , because the differences in ratings are the greatest for the " people aspects " of care , if improvement efforts are prioritized on the basis of these rapid results , the wrong priorities may be set The purpose was to evaluate low-dose CT colonography without cathartic cleansing in terms of image quality , polyp visualization and patient acceptance . Sixty-one patients scheduled for colonoscopy started a low-fiber diet , lactulose and amidotrizoic-acid for fecal tagging 2 days prior to the CT scan ( st and ard dose , 5.8–8.2 mSv ) . The original raw data of 51 patients were modified and reconstructed at simulated 2.3 and 0.7 mSv levels . Two observers evaluated the st and ard dose scan regarding image quality and polyps . A third evaluated the presence of polyps at all three mSv levels in a blinded prospect i ve way . All observers were blinded to the reference st and ard : colonoscopy . At three times patients were given question naires relating to their experiences and preference . Image quality was sufficient in all patients , but significantly lower in the cecum , sigmoid and rectum . The two observers correctly identified respectively 10/15 ( 67 % ) and 9/15 ( 60 % ) polyps ≥10 mm , with 5 and 8 false-positive lesions ( st and ard dose scan ) . Dose reduction down to 0.7 mSv was not associated with significant changes in diagnostic value ( polyps ≥10 mm ) . Eighty percent of patients preferred CT colonography and 13 % preferred colonoscopy ( P<0.001 ) . CT colonography without cleansing is preferred to colonoscopy and shows sufficient image quality and moderate sensitivity , without impaired diagnostic value at dose-levels as low as 0.7 mSv OBJECTIVES : Visualizing the entire colorectum in screening is an advantage of colonoscopy , and also computed tomographic ( CT ) colonography , another potentially suitable screening test . Our objective was to compare screening CT colonography and colonoscopy in an asymptomatic average-risk population , and to determine whether providing a choice of tests increased participation . METHODS : One thous and and four hundred subjects from the general community , r and omly selected from the parliamentary electoral roll , were allocated one of three screening groups : colonoscopy , CT colonography , or a choice of these tests , and were sent an institutional letter of invitation . Those with symptoms , colorectal cancer in first-degree relatives , or colonoscopy within 5 yr were ineligible . Outcome measures were participation , acceptability of screening , and yield for advanced colorectal neoplasia in participants . RESULTS : Of the subjects , 24.9 % were ineligible ; the overall participation rate was 18.2 % ( 184/1,009 ) . Participation in each screening group was not different . Both tests were accompanied by the same high levels of acceptability ; most participants found colonoscopy ( 87 % ) and CT colonography ( 67 % , p < 0.001 ) less unpleasant than expected . About 29 % ( 26/89 ) CT colonography subjects had a positive screening test . The yield of advanced colorectal neoplasia was 8.7 % ( 95 % CI 5–14 % ) , with no difference in yield between tests . CONCLUSION : Colorectal neoplasia screening by colonoscopy or CT colonography was associated with modest participation , high levels of acceptability , and similar yield for advanced colorectal neoplasia . Providing a choice of test did not increase participation Background : Patient satisfaction surveys are widely used to measure patients ’ opinions of the quality of the health care they have received . There are a variety of methods for distributing patient satisfaction surveys . Different distribution methods may yield significantly different satisfaction ratings . Objective : We sought to compare survey ratings obtained via 2 distribution methods : h and out versus mailed . Design : Patients were r and omized to receive either a h and out survey or a mailed survey . Subjects : Patients who had an appointment with a family practice provider in one of the regional outpatient centers of a large medical clinic during a 3-week period . Measures : An 11-item visit-specific patient satisfaction survey was used to survey patient satisfaction . Results : H and out surveys yielded higher satisfaction scores than mailed surveys . The response rate was higher with h and out surveys than with mailed surveys . However , h and out surveys were returned with more skipped questions , a lower variation in ratings , and fewer written comments than the mailed surveys . Conclusions : Both quantitative and qualitative differences between the 2 distribution methods were revealed . Attempts to compare data obtained from the 2 different distribution methods need to be approached with caution To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography ( CTC ) . Ninety-five subjects underwent reduced-laxative ( 13 g senna/18 g magnesium citrate ) CTC prior to same-day colonoscopy and were r and omised to one of four tagging regimens using 20 ml 40%w/v barium sulphate : regimen A : four doses , B : three doses , C : three doses plus 220 ml 2.1 % barium sulphate , or D : three doses plus 15 ml diatriazoate megluamine . Patient experience was assessed immediately after CTC and 1 week later . Two radiologists grade d residual stool ( 1 : none/scattered to 4 : > 50 % circumference ) and tagging efficacy for stool ( 1 : untagged to 5 : 100 % tagged ) and fluid ( 1 : untagged , 2 : layered , 3 : tagged ) , noting the HU of tagged fluid . Preparation was good ( 76–94 % segments grade d 1 ) , although best for regimen D ( P = 0.02 ) . Across all regimens , stool tagging quality was high ( mean 3.7–4.5 ) and not significantly different among regimens . The HU of layered tagged fluid was higher for regimens C/D than A/B ( P = 0.002 ) . Detection of cancer ( n = 2 ) , polyps ≥6 mm ( n = 21 ) , and ≤5 mm ( n = 72 ) was 100 , 81 and 32 % respectively , with only four false positives ≥6 mm . Reduced preparation was tolerated better than full endoscopic preparation by 61 % . Reduced-laxative CTC with three doses of 20 ml 40 % barium sulphate is as effective as more complex regimens , retaining adequate diagnostic accuracy Background Decision aids can improve decision making processes , but the amount and type of information that they should attempt to communicate is controversial . We sought to compare , in a pilot r and omized trial , two colorectal cancer ( CRC ) screening decision aids that differed in the number of screening options presented . Methods Adults ages 48–75 not currently up to date with screening were recruited from the community and r and omized to view one of two versions of our previously tested CRC screening decision aid . The first version included five screening options : fecal occult blood test ( FOBT ) , sigmoidoscopy , a combination of FOBT and sigmoidoscopy , colonoscopy , and barium enema . The second discussed only the two most frequently selected screening options , FOBT and colonoscopy . Main outcomes were differences in screening interest and test preferences between groups after decision aid viewing . Patient test preference was elicited first without any associated out-of-pocket costs ( OPC ) , and then with the following costs : FOBT-$10 , sigmoidoscopy-$50 , barium enema-$50 , and colonoscopy-$200 . Results 62 adults participated : 25 viewed the 5-option decision aid , and 37 viewed the 2-option version . Mean age was 54 ( range 48–72 ) , 58 % were women , 71 % were White , 24 % African-American ; 58 % had completed at least a 4-year college degree . Comparing participants that viewed the 5-option version with participants who viewed the 2-option version , there were no differences in screening interest after viewing ( 1.8 vs. 1.9 , t-test p = 0.76 ) . Those viewing the 2-option version were somewhat more likely to choose colonoscopy than those viewing the 5-option version when no out of pocket costs were assumed ( 68 % vs. 46 % , p = 0.11 ) , but not when such costs were imposed ( 41 % vs. 42 % , p = 1.00 ) . Conclusion The number of screening options available does not appear to have a large effect on interest in colorectal cancer screening . The effect of offering differing numbers of options may affect test choice when out-of-pocket costs are not considered OBJECTIVE Colorectal cancer ( CRC ) screening uptake remains poor . Until we underst and patient motivation and preferences for undertaking screening , it is unlikely the uptake will be optimal . Our objective is to examine patient preferences for CRC screening modalities and uptake rates using utility-based methods . METHODS The preference survey was mailed to a r and om sample of Canadian subjects aged 40 to 60 years from a primary care network . A fractional factorial experimental design maximized D-efficiency and included four blocks with 12 choice tasks in a conditional two-step design , two-alternative discrete choice format with five screening attributes ( process , pain , preparation , sensitivity , and specificity ) . Bivariate probit regression analysis was used to estimate patient preferences for attributes , choice probabilities for alternative modalities and expected rates of uptake . RESULTS Five hundred forty-seven of 1047 surveys were returned . Almost 30 % of respondents preferred no screening . The most preferred test attribute levels were noninvasive process ( e.g. , CT ) , no preparation , no pain , 100 % specificity , and 90 % sensitivity . Accuracy-related attributes were more important than test process-related attributes . Virtual colonoscopy was the most preferred , followed by colonoscopy , barium enema , sigmoidoscopy , and fecal DNA testing , based on simulated choice probability estimates . Fecal occult blood testing ( FOBT ) was least preferred . Adjusted screening uptake rate estimates showed the greatest impact ( 42 % increase ) would be achieved if all CRC screening modalities were available rather than FOBT alone . CONCLUSIONS Our findings emphasize the important role of patient preferences for no screening and in selecting alternative CRC screening modalities . CRC screening implementation in Canada should consider patient preferences to optimize uptake PURPOSE To prospect ively evaluate , by means of self-assessed question naires , patient acceptance of computed tomographic ( CT ) colonography compared with that of conventional colonoscopy , when performed in patients with or suspected of having colorectal disease . MATERIAL S AND METHODS One hundred eleven patients underwent CT colonography followed immediately by conventional colonoscopy . Patient acceptance was evaluated with question naires , and the proportions of patients who favored one examination were compared . The main variables were overall impression , discomfort during air filling or instrumentation , and perceived pain , evaluated by using ordered verbal descriptor scales after each examination . The preference for either examination was evaluated after completion of both examinations . RESULTS Of the 68 patients who favored one examination , 56 ( 82 % ) preferred CT colonography ( P < .00001 ) . Concerning overall impression of problems or discomfort in connection with the examination , 49 ( 69 % ) of 71 with a preference considered colonoscopy to be more difficult ( P = .002 ) . CT colonography was regarded as " not painful " by 62 ( 57 % ) of 108 patients compared with 28 ( 26 % ) for colonoscopy , and a larger proportion of patients rated pain as higher during colonoscopy than during CT colonography ( 95 % CI : 30 % , 56 % ) . Discomfort from air filling of the colon was the major complaint about CT colonography . CONCLUSION CT colonography was considered less painful and less difficult overall than colonoscopy and was the preferred examination OBJECTIVE Conventional colonoscopy ( CC ) is the gold st and ard for colonic examinations . However , patient acceptance is not high . Patient acceptance is influenced by several factors , notably anticipation and experience . This has led to the assumption that patient acceptance would be higher in non-invasive examinations such as MR/CT colonography ( MRC/CTC ) and perhaps even higher without bowel preparation . The purpose of this study was to evaluate patient acceptance of MRC with fecal tagging versus CC . MATERIAL S AND METHODS In a 14-month period , all patients first-time referred to our department for CC were asked to participate in the study . Two days prior to MRC , patients ingested an oral contrast mixture ( barium/ferumoxsil ) together with four meals each day . St and ard bowel purgation was performed before CC . Before and after MRC and CC a number of questions were addressed . RESULTS Sixty-four ( 34 men , 30 women ) patients referred for CC participated in the study . 27 % had some discomfort ingesting the contrast mixture , and 49 % had some discomfort with the bowel purgation . As a future colonic examination preference , 71 % preferred MRC , 13 % preferred CC and 15 % had no preference . If MRC was to be performed with bowel purgation , 75 % would prefer MRC , 12 % would prefer CC and 12 % had no preference . CONCLUSION This study shows that there is a potential gain in patient acceptance by using MRC for colonic examination , since MRC is considered less painful and less unpleasant than CC . In addition , the results indicate that patients in this study prefer fecal tagging instead of bowel purgation PURPOSE To prospect ively evaluate participants ' experience and preference of magnetic resonance ( MR ) colonography with limited bowel preparation compared with full-preparation colonoscopy in participants at increased risk for colorectal cancer . MATERIAL S AND METHODS This study had institutional review board approval ; all participants gave written informed consent . In this multicenter study , consecutive participants undergoing conventional colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps underwent MR colonography 2 weeks prior to colonoscopy . They all followed a low-fiber diet and were given lactulose and an oral contrast agent ( fecal tagging with gadolinium ) 2 days before colonography . Before imaging , spasmolytics were administered intravenously , and a water-gadolinium chelate mixture was administered rectally for distention of the colon . Breath-hold T1- and T2-weighted sequences were performed in the prone and supine positions . Participant experience in terms of , for example , pain and burden was determined by using a five-point scale and was evaluated with a Wilcoxon signed rank test ; participant preference was determined by using a seven-point scale and was evaluated with the chi2 statistic after dichotomizing . RESULTS Two hundred nine participants ( 77 women , 132 men ; mean age , 58 years ; range , 23 - 84 years ) were included . One hundred forty-eight participants received sedatives ( midazolam ) and /or analgesics ( fentanyl ) during colonoscopy . Participants rated the MR colonography bowel preparation as less burdensome ( P<.001 ) compared with the colonoscopy bowel preparation ( 10 % and 71 % of participants rated the respective examinations moderately to extremely burdensome ) . Participants also experienced less pain at MR colonography ( P<.001 ) and found MR colonography less burdensome ( P<.001 ) . Immediately after both examinations , 69 % of participants preferred MR colonography , 22 % preferred colonoscopy , and 9 % were indifferent ( P<.001 , 69 % vs 22 % ) . After 5 weeks , 65 % preferred MR colonography and 26 % preferred colonoscopy ( P<.001 ) . CONCLUSION Participants preferred MR colonography without extensive cleansing to colonoscopy immediately after both examinations and 5 weeks later . Experience of the bowel preparation and of the procedure was rated better PURPOSE To prospect ively evaluate short- and midterm patient preference of computed tomographic ( CT ) colonography relative to colonoscopy in patients at increased risk for colorectal cancer and to eluci date determinants of preference . MATERIAL S AND METHODS Consecutive patients at increased risk for colorectal cancer underwent CT colonography prior to scheduled colonoscopy . Patient experience and preference were assessed both directly after the examinations and 5 weeks after the examinations . Differences in pain , embarrassment , discomfort , and preference were assessed with the Wilcoxon signed rank sum test or a binomial test . Potential determinants of preference were investigated with logistic regression analyses . RESULTS Data for 249 patients were included . Fewer patients experienced severe or extreme pain during CT colonography ( seven [ 3 % ] of 245 ) than during colonoscopy ( 81 [ 34 % ] of 241 ) ( P < .001 ) . Directly after both examinations , 168 ( 71 % ) of 236 patients preferred CT colonography ; 5 weeks later , 141 ( 61 % ) of 233 patients preferred CT colonography ( P < .001 ) . Initially , a painful colonoscopy examination ( odds ratio , 0.17 ; 95 % confidence interval [ CI ] : 0.08 , 0.38 ) was a determinant of CT colonography preference . Similarly , a painful ( odds ratio , 3.70 ; 95 % CI : 1.54 , 8.92 ) or an embarrassing ( odds ratio , 4.46 ; 95 % CI : 1.18 , 16.88 ) CT colonography examination was a determinant of colonoscopy preference . After 5 weeks , the presence of polyps emerged as a determinant of colonoscopy preference ( odds ratio , 1.94 ; 95 % CI : 1.02 , 3.70 ) , while the role of experiences waned . CONCLUSION Patients preferred CT colonography to colonoscopy ; however , this preference decreased in time , while outcome considerations gradually replaced temporary experiences of inconvenience Objective Virtual colonoscopy (VC)/CT colonography has advantages over the well‐documented limitations of colonoscopy/barium enema . This prospect i ve blinded investigative comparison trial aim ed to evaluate the ability of VC to assess the large bowel , compared to conventional colonoscopy ( CC ) , in patients at high risk of colorectal cancer ( CRC ) RATIONALE AND OBJECTIVES To compare prospect ively 64-detector-row computed tomographic colonography ( CTC ) after a full-laxative tagging-based preparation ( full preparation ) with a minimum-laxative tagging-based preparation ( minimum preparation ) with respect to diagnostic performance in the detection of polyps , tagging quality , and patient acceptance . MATERIAL S AND METHODS Consecutive 101 patients at high risk for developing colorectal cancer were alternately assigned to either a full preparation group ( n = 51 ) or a minimum preparation group ( n = 50 ) for fecal-tagging CTC . The full preparation consisted of administration of 2-L polyethylene glycol solution with 20 mL of sodium diatrizoate for fecal tagging . The minimum preparation consisted of ingestion of a total of 45 mL of sodium diatrizoate during the 3 days before and 10 mL of sodium picosulfate solution the night before CT . Colonoscopy was used as the reference st and ard . We assessed the accuracy of polyp detection and the tagging quality for each preparation . All patients were given question naires related to their acceptance . RESULTS Per-patient sensitivity , specificity , and positive and negative predictive values for polyps > or = 6 mm were as follows : full preparation group , 97 % , 92 % , 88 % , and 98 % , respectively ; minimum preparation group , 88 % , 68 % , 56 % , and 92 % , respectively . Average visual subjective tagging scores for the full and minimum preparation groups were 94.6 % and 76.1 % , respectively ( P < .0001 ) . Minimum preparation was better tolerated than full preparation . CONCLUSION Although full-laxative and minimum-laxative fecal-tagging CTC yielded an equally high sensitivity in the detection of polyps > or = 6 mm , the full-laxative fecal-tagging CTC yielded a better specificity than did the minimum-laxative fecal-tagging CTC . Thus , it is desirable to offer patients an option of either full-laxative fecal-tagging CTC for highest diagnostic accuracy and ability to perform a same-day therapeutic colonoscopy without additional bowel preparation , or minimum-laxative fecal-tagging CTC for those unwilling to undergo full preparation but willing to accept moderate decrease in specificity PURPOSE To prospect ively assess and compare perceptions of and preferences for computed tomographic ( CT ) colonography , colonoscopy , and double-contrast barium enema examination ( DCBE ) by asymptomatic patients undergoing colorectal cancer screening . MATERIAL S AND METHODS A total of 696 asymptomatic patients at higher-than-average risk undergoing colorectal cancer screening were consecutively recruited to undergo both CT colonography and colonoscopy ( group 1 ) , and a like group of 617 patients was separately recruited to undergo both CT colonography and DCBE ( group 2 ) . St and ard bowel preparations were different between the groups undergoing colonoscopy and DCBE . Each patient completed a question naire that assessed preparation inconvenience and discomfort , examination discomfort , willingness to repeat examinations , and examination preference . Survey results were compared for significance by using the Wilcoxon rank sum or chi2 test . RESULTS The majority of patients considered the preparation to be uncomfortable ( group 1 , 460 of 515 [ 89 % ] ; group 2 , 482 of 538 [ 90 % ] ) and inconvenient ( group 1 , 393 of 502 [ 78 % ] ; group 2 , 427 of 527 [ 81 % ] ) . Reported discomfort was similar at CT colonography and colonoscopy ( P = .63 ) but was less at CT colonography than at DCBE ( P < .001 ) . Patients experienced significantly less discomfort than expected at both CT colonography and colonoscopy but not at DCBE . Patients ' willingness to undergo frequent rescreening was significantly greater for CT colonography than for either colonoscopy or DCBE . The acceptable time interval between screenings was significantly shorter for all examinations if the bowel preparation could be avoided . Overall , patients preferred CT colonography to colonoscopy ( group 1 , 72.3 % vs 5.1 % ; P < .001 ) or to DCBE ( group 2 , 97.0 % vs 0.4 % ; P < .001 ) . CONCLUSION Patients undergoing colorectal cancer screening prefer CT colonography to both colonoscopy and DCBE . The majority of patients experience discomfort and inconvenience with cathartic bowel preparation Abstract . The purpose of this study was to evaluate the feasibility of a dry bowel preparation , i.e. without laxative fluids , for virtual CT colonography ( VCTC ) , and its impact on patient acceptance compared with conventional colonoscopy ( CC ) . A r and omly chosen patient population scheduled for CC ( n=11 ) was first su bmi tted to VCTC after a dry preparation , consisting of low-residue meals combined with a small amount of a iodinated water-soluble contrast medium during each meal 3 days before VCTC . In different colon segments and between different persons , the degree of tagging in VCTC was evaluated and grade d. Patient acceptance and future preference were assessed for both preparations as well as for both investigations . The mixing of the contrast with the intestinal content results in contrast impregnated stool , the tagged feces . The degree of fecal tagging was good in the majority of the patients and the colonic segments , especially in the descending colon and sigmoid . Furthermore , patient acceptance and preference were clearly in favour of VCTC compared with CC merely because of the non-invasiveness of the dry preparation . Dry bowel preparation and VCTC is a promising approach towards a patient-friendly colon cancer-screening setup OBJECTIVE The purpose of our study was to prospect ively evaluate image quality and patient acceptance of CT colonography ( CTC ) with fecal tagging using different levels of catharsis . SUBJECTS AND METHODS Forty consecutive increased-risk patients were r and omized . Group 1 received orally 20 mg of bisacodyl , group 2 received 30 mg of bisacodyl , group 3 received 20 mg of bisacodyl and 8.2 g of magnesium citrate , and group 4 received 30 mg of bisacodyl and 16.4 g of magnesium citrate . All patients used a 2-day low-fiber diet and received diatrizoate meglumine and barium for fecal tagging . One review er blindly scored subjective image quality ( fecal tagging , amount of residual feces [ liquid or solid ] , luminal distention , and image readability ) on a 5- to 6-point scale using a 2D review technique . The mean and SD of attenuation of tagging were measured as well as the relative SD as a measure of homogeneity . Furthermore , patient acceptance ( burden related to diarrhea , abdominal pain , flatulence , and overall burden ) was evaluated . Ordinal regression , generalized estimating equations , and parametric and nonparametric tests were used for analysis . RESULTS Image readability was evaluated as good or excellent in all examinations except one in group 2 ( nondiagnostic ) and two in group 3 ( moderate ) . Group 2 contained more feces than group 4 ( p = 0.04 ) . With regard to mean attenuation and homogeneity of tagging , no significant differences were observed between groups . Group 4 experienced more severe diarrhea than groups 1 and 2 and higher overall burden than groups 1 and 3 ( p < 0.042 ) . CONCLUSION The mildest preparation with 20 mg of bisacodyl provided good image quality of CTC images . Increasing the amount of laxatives did not improve image quality or tagging characteristics but was associated with a lower patient acceptance Background and aims : This prospect i ve trial was design ed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia : CT colonography ( CTC ) , colonoscopy ( OC ) , flexible sigmoidoscopy ( FS ) , faecal immunochemical stool testing ( FIT ) and faecal occult blood testing ( FOBT ) . Methods : Average risk adults provided stool specimens for FOBT and FIT , and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the st and ard of reference . Sensitivities and specificities were calculated for each single test , and for combinations of FS and stool tests . CTC radiation exposure was measured , and patient comfort levels and preferences were assessed by question naire . Results : 221 adenomas were detected in 307 subjects who completed CTC ( mean radiation dose , 4.5 mSv ) and OC ; 269 patients provided stool sample s for both FOBT and FIT . Sensitivities of OC , CTC , FS , FIT and FOBT for advanced colonic neoplasia were 100 % ( 95 % CI 88.4 % to 100 % ) , 96.7 % ( 82.8 % to 99.9 % ) , 83.3 % ( 95 % CI 65.3 % to 94.4 % ) , 32 % ( 95 % CI 14.9 % to 53.5 ) and 20 % ( 95 % CI 6.8 % to 40.7 % ) , respectively . Combination of FS with FOBT or FIT led to no relevant increase in sensitivity . 12 of 45 advanced adenomas were smaller than 10 mm . 46 % of patients preferred CTC and 37 % preferred OC ( p<0.001 ) . Conclusions : High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps > 5 mm . For patients who refuse full bowel preparation and OC or CTC , FS should be preferred over stool tests . However , in cases where stool tests are performed , FIT should be recommended rather than FOBT PURPOSE To prospect ively compare the homogeneity , adequacy , and patient acceptance of nonionic iodine-based regimens with those of a barium-based regimen for computed tomographic ( CT ) colonography with electronic subtraction cleansing . MATERIAL S AND METHODS After institutional review board approval and informed consent were obtained , 68 subjects ( 41 men ( 60 % ) men , 27 ( 40 % ) women ; mean age , 60 years + /- 6 [ st and ard deviation ] ) with average or moderate risk factors for development of colorectal carcinoma were recruited and placed into three study groups . Group 1 ( n = 25 ) ingested 150-mL aliquots of 2 % barium sulfate suspension with meals and snacks for 48 hours prior to imaging , without other diet modification or a cathartic . Group 2 ( n = 21 ) ingested 10-mL aliquots of nonionic iodinated contrast material ( iopromide ) with a concentration of 300 mg per milliliter with meals and snacks for 2 days before imaging , without diet modification or a cathartic . Group 3 ( n = 22 ) ingested nonionic iodinated contrast material ( iohexol ) with a concentration of 300 mg per milliliter with meals and snacks for 2 days before imaging and ingested 34 g of magnesium citrate the evening prior to imaging . CT colonography was also performed on 10 control subjects who ingested polyethylene glycol electrolyte solution prior to imaging . Subjective and numerical measures of bowel preparation quality , homogeneity , and patient comfort among the noncathartic and cathartic cohorts were compared with nonparametric analysis of variance , the Fisher exact test , and the F test , as appropriate . The study was HIPAA compliant . RESULTS Study subjects who received tagging preparations reported significantly improved discomfort scores when compared with those of the control subjects ( P < .05 , each comparison ) . There was no significant difference in discomfort scores among groups 1 , 2 , and 3 . For each reader , scores of subtracted image readability were highest for group 3 . Dichotomized rates of preparation " success " were also greatest for group 3 . CONCLUSION In this series , the patient discomfort scores were significantly improved with tagging preparations for CT colonography . Nonionic iodinated contrast material in conjunction with a hyperosmotic laxative ( magnesium citrate ) was associated with the best subjective and numerical indices of readability CT colonography without bowel preparation is a safer and better-tolerated alternative to full laxation protocol s , but comparative sensitivity and specificity are potentially reduced . Uptake of 18F-FDG by colonic neoplasia is well described , and combining PET with nonlaxative CT colonography could improve accuracy . The purpose was to prospect ively test the technical feasibility and acceptability of combined nonlaxative PET/CT colonography in patients at higher risk of colorectal neoplasia and to provide pilot data on diagnostic performance . Methods : Fifty-six patients ( median age , 64 y ; 30 women ) at high risk of colonic neoplasia underwent nonlaxative PET/CT colonography with barium fecal tagging within 2 wk of scheduled colonoscopy . Colonic segmental distension was grade d 1 ( poor ) to 3 ( good ) . A radiologist , experienced in CT colonography , and nuclear medicine physician in consensus analyzed the data sets . The diagnostic performance for st and alone CT colonography and combined PET/CT colonography was compared with the reference colonoscopy . Patient experience for 25 items ( each scored from 1 to 7 ) pertaining to satisfaction , worry , and physical discomfort was canvassed after both PET/CT colonography and colonoscopy . Results : Distension was good in 298 of 334 segments ( 89 % ; 95 % confidence interval [ CI ] , 85%−92 % ) . Patients experienced more physical discomfort during colonoscopy ( median , 4 ; interquartile range [ IQR ] , 2–7 ) than during PET/CT colonography ( median , 5 ; IQR , 3–7 ; P = 0.03 ) and were more willing to undergo PET/CT colonography again ( 36/43 [ 84 % ; 95 % CI , 73%−95 % ] vs. 31/43 [ 72 % ; 95 % CI , 59%−86 % ] ; P = 0.001 ) . Twenty-one patients had 54 polyps according to colonoscopy ( 10 with at least 1 polyp ≥6 mm and 8 with at least 1 polyp ≥10 mm ) . Of 14 polyps 6 mm or greater , 12 ( 86 % ; 95 % CI , 67%−100 % ) were 18F-FDG – avid , including all those 10 mm or greater ( mean st and ardized uptake value , 10.1 ) . CT colonography sensitivity for polyps 6 mm or larger was 92.9 % ( 95 % CI , 79.4%−100 % ) and was not improved by the addition of PET . However , combined PET/CT colonography review improved per-patient positive predictive value for a polyp 10 mm or greater from 73 % ( 95 % CI , 39–92 ) to 100 % ( 95 % CI , 60–100 ) . Conclusion : In this feasibility study , simultaneous PET acquisition during nonlaxative CT colonography is technically feasible , is well tolerated , and potentially improves specificity |
433 | 23,220,130 | Lower weight gain in the low fat arm compared with the control arm was consistent across trials , but the size of the effect varied .
Metaregression suggested that greater reduction in total fat intake and lower baseline fat intake were associated with greater relative weight loss , explaining most of the heterogeneity .
The significant effect of a low fat diet on weight was not lost in sensitivity analyses ( including removing trials that expended greater time and attention on low fat groups ) .
GRADE assessment suggested high quality evidence for the relation between total fat intake and body weight in adults .
There is high quality , consistent evidence that reduction of total fat intake has been achieved in large numbers of both healthy and at risk trial participants over many years .
Evidence supports a similar effect in children and young people | OBJECTIVE To investigate the relation between total fat intake and body weight in adults and children . | The Minnesota Coronary Survey was a 4.5-year , open enrollment , single end-time , double-blind , r and omized clinical trial that was conducted In six Minnesota state mental hospitals and one nursing home . It Involved 4393 Institutionalized men and 4664 Institutionalized women . The trial compared the effects of a 39 % fat control diet ( 18 % saturated fat , 5 % polyunsaturated fat , 16 % monounsaturated fat , 446 mg dietary cholesterol per day ) with a 38 % fat treatment diet ( 9 % saturated fat , 15 % polyunsaturated fat , 14 % monounsaturated fat , 166 mg dietary cholesterol per day ) on serum cholesterol levels and the Incidence of myocardlal Infa rct ions , sudden deaths , and all-cause mortality . The mean duration of time on the diets was 384 days , with 1568 subjects consuming the diet for over 2 years . The mean serum cholesterol level In the pre-admission period was 207 mg/dl , falling to 175 mg/dl in the treatment group and 203 mg/dl In the control group . For the entire study population , no differences between the treatment and control groups were observed for cardiovascular events , cardiovascular deaths , or total mortality . A favorable trend for all these end-points occurred In some younger age groups CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 BACKGROUND Dietary factors and very-long-chain n-3 polyunsaturated fatty acids ( n-3 PUFAs ) may influence the atherothrombotic process . Elevated concentrations of circulating cell adhesion molecules , thrombomodulin ( TM ) , von Willebr and factor ( vWF ) , and tissue-type plasminogen activator antigen ( tPAag ) are related to atherothrombotic cardiovascular disease . OBJECTIVE The r and omized Diet and Omega-3 Intervention Trial ( DOIT ) targeted a comparison of the effect of 3-y dietary counseling , n-3 PUFA supplementation ( 2.4 g/d ) , or both on circulating markers of endothelial activation . DESIGN The study included 563 elderly men with long-st and ing hyperlipidemia . The men were r and omly assigned by factorial design into 4 groups : control ( no dietary counseling and placebo capsules ) , dietary counseling ( and placebo capsules ) , n-3 PUFA supplementation ( no dietary counseling ) , and dietary counseling and n-3 PUFA supplementation . RESULTS Serum concentrations of fatty acids reflected good compliance . Dietary counseling was followed by significantly reduced concentrations of soluble intercellular adhesion molecule 1 ( sICAM-1 ; P < 0.001 ) , sTM ( P = 0.004 ) , and tPAag ( P < 0.001 ) than in subjects without dietary counseling . After n-3 PUFA supplementation , significantly reduced concentrations of sICAM-1 ( P < 0.001 ) and sTM ( P = 0.006 ) were observed when compared with subjects receiving placebo capsules . An increase in tPAag was not significantly different from that observed in subjects receiving placebo capsules . For sICAM-1 , a significant effect was observed for both interventions combined . CONCLUSIONS Each intervention ( dietary counseling or n-3 PUFA supplements ) reduced sTM and sICAM-1 concentrations , indicating decreased endothelial activation . The tPAag increase in the groups not receiving dietary counseling ( pooled ) , which indicates progression of atherosclerosis , was significantly counteracted by dietary counseling Effects of specific dietary alterations in patients with radiolucent gallstones treated with ursodeoxycholic acid ( UDCA , 750 mg at bedtime ) were investigated . Patients were allocated r and omly to one of four diets : st and ard ( 500 mg cholesterol/day ) , low-cholesterol ( 250 mg/day ) , added-bran ( 30 g/day ) , or substituted medium-chain triglycerides ( MCT ) oil ( 20 % of fat ) . Dietary intake and good compliance were verified by computerized analysis of dietary diaries . Bile-acid kinetics ( 26 patients ) or secretion of biliary lipids ( 23 other patients ) were determined at enrollment and at 6 and 9 mo , respectively , during treatment . Although MCT further decreased the UDCA-induced decrease in the synthesis of chenodeoxycholic acid , it did not lessen desaturation of bile . Otherwise , compared to the st and ard diet , no experimental diet significantly altered the UDCA-induced increase of the pools of total bile acids and UDCA or the UDCA-induced decrease in synthesis of bile acids and in biliary secretion or saturation of cholesterol . If these dietary manipulations facilitate dissolution of gallstones by UDCA , they do so by other mechanisms BACKGROUND The optimal dietary content and type of fat and carbohydrate for weight management has been debated for decades . OBJECTIVE The objective was to compare the effects of 3 ad libitum diets on the maintenance of an initial weight loss of > or=8 % and risk factors for CVD and diabetes during a 6-mo controlled dietary intervention . DESIGN Nondiabetic overweight or obese [ mean + /- SD body mass index ( in kg/m(2 ) ) : 31.5 + /- 2.6 ] men ( n = 55 ) and women ( n = 76 ) aged 28.2 + /- 4.8 y were r and omly assigned to a diet providing a moderate amount of fat ( 35 - 45 % of energy ) and > 20 % of fat as monounsaturated fatty acids ( MUFA diet ; n = 54 ) , to a low-fat ( 20 - 30 % of energy ) diet ( LF diet ; n = 51 ) , or to a control diet ( 35 % of energy as fat ; n = 26 ) . Protein constituted 10 - 20 % of energy in all 3 diets . All foods were provided free of charge from a purpose -built supermarket . RESULTS More subjects dropped out of the MUFA ( 28 % ) group than out of the LF group ( 16 % ) and control group ( 8 % ) ( MUFA compared with control : P < 0.05 ) . All groups regained weight ( MUFA : 2.5 + /- 0.7 kg ; LF : 2.2 + /- 0.7 kg ; and control : 3.8 + /- 0.8 kg ; NS ) . Body fat regain was lower in the LF ( 0.6 + /- 0.6 % ) and MUFA ( 1.6 + /- 0.6 % ) groups than in the control group ( 2.6 + /- 0.5 % ) ( P < 0.05 ) . In the MUFA group , fasting insulin decreased by 2.6 + /- 3.5 pmol/L , the homeostasis model assessment of insulin resistance by 0.17 + /- 0.13 , and the ratio of LDL to HDL by 0.33 + /- 0.13 ; in the LF group , these variables increased by 4.3 + /- 3.0 pmol/L ( P < 0.08 ) and 0.17 + /- 0.10 ( P < 0.05 ) and decreased by 0.02 + /- 0.09 ( P = 0.005 ) , respectively ; and in the control group , increased by 14.0 + /- 4.3 pmol/L ( P < 0.001 ) , 0.57 + /- 0.17 ( P < 0.001 ) , and 0.05 + /- 0.14 ( P = 0.036 ) , respectively . Dietary adherence was high on the basis of fatty acid changes in adipose tissue . CONCLUSIONS Diet composition had no major effect on preventing weight regain . However , both the LF and MUFA diets produced less body fat regain than did the control diet , and the dropout rate was lowest in the LF diet group , whereas fasting insulin decreased and the homeostasis model assessment of insulin resistance and ratio of LDL to HDL improved with the MUFA diet . This trial was registered at clinical trials.gov as NCT00274729 BACKGROUND Dietary fat has been implicated as a risk factor for cardiovascular disease and obesity . OBJECTIVE We evaluated the effect on body weight , body fat , lipids , glucose , and insulin of replacing dietary fat with olestra in moderately obese men . DESIGN Forty-five healthy overweight men were r and omly assigned to 1 of 3 diets : control diet ( 33 % fat ) , fat-reduced diet ( 25 % fat ) , or fat-substituted diet ( one-third of dietary fat replaced by olestra to achieve a diet containing 25 % metabolizable fat ) . Body fat was measured by dual-energy X-ray absorptiometry and visceral and subcutaneous abdominal fat by computed tomography . RESULTS Thirty-six men completed the 9-mo study . Body weight and body fat in the fat-substituted group declined by a mean ( + /- SEM ) of 6.27 + /- 1.66 and 5.85 + /- 1.34 kg , respectively , over 9 mo compared with 3.8 + /- 1.34 and 3.45 + /- 1.0 kg in the control group and 1.79 + /- 0.81 and 1.68 + /- 0.75 kg in the fat-reduced diet group . At 9 mo , the mean difference in body fat between the fat-reduced and fat-substituted groups was -4.19 + /- 1.19 kg ( 95 % CI : -6.57 , -1.81 ) , that between the control and fat-substituted groups was -2.55 + /- 1.21 kg ( -0.13 , -4.97 ) , and that between the control and fat-reduced groups was 1.63 + /- 1.18 kg ( 3.96 , -0.70 ) . The men eating the fat-reduced diet asked for almost no extra foods , in contrast with the significantly higher requests ( P < 0.05 ) from both of the other 2 groups . CONCLUSION Replacement of dietary fat with olestra reduces body weight and total body fat when compared with a 25%-fat diet or a control diet containing 33 % fat This r and omised controlled trial examined anthropometric changes and cardiovascular benefits of six months of weight management in 110 free living women , aged 18–68 y and BMI 25–50 kg/m2 , who received 1200 kcal/d diet treatments of either high ( 58 % energy , n=57 ) or low ( 35 % energy , n=53 ) carbohydrate ( CHO ) content . Body weight , plasma total , HDL and LDL cholesterol , triglyceride and blood pressure were measured . Examination at three months showed women on high CHO lost ( mean±s.e.m . ) 4.3±0.5 kg and those on low CHO lost 5.6±0.6 kg of body weight . Changes in risk factors did not significantly differ between the two diet treatments throughout the study . However those on high CHO diets significantly lowered their plasma total cholesterol by 0.33 mmol/l ( 95 % CI : 0.10 , 0.55 ) , LDL cholesterol by 0.23 mmol/l ( 0.02 , 0.43 ) and HDL cholesterol by 0.05 mmol/l ( 0.03 , 0.10 ) , while women on low CHO diets lowered only plasma triglyceride by 0.28 mmol/l ( 0.08 , 0.48 ) . Blood pressure did not change significantly on either diet . After six months , women on high CHO lost 5.6±0.8 kg and those on low CHO lost 6.8±0.8 kg . On the high CHO diet , total cholesterol remained significantly below the baseline value at 0.34 mmol/l ( 0.13 , 0.56 ) , triglyceride was significantly lowered by 0.27 mmol/l ( 0.10 , 0.45 ) , and HDL cholesterol returned to the baseline value . On the low CHO diet , triglyceride remained the only risk factor to be significantly improved . A subgroup of 46 postmenopausal women lost significantly ( P<0.05 ) more weight on the low CHO diet than high CHO diet . In conclusion , these results provided some support for preferring a high CHO diet to a lower CHO approach in weight management , from the point of view of risk reduction , but do not indicate a consistently more rapid weight loss with either diet We are conducting a long-term r and omized controlled trial to determine if intervention with a low-fat high-carbohydrate diet reduces breast cancer risk . The present study examines the effects of 2 years of dietary intervention on serum sex hormone levels in premenopausal women . Subjects with extensive mammographic densities were enrolled in a dietary intervention trial . The intervention involved intensive individual counselling aim ed at reducing total dietary fat to 15 % of calories . Control subjects received general advice about diet but were not counselled to change their fat intake . Serum sex hormone levels were measured in 220 premenopausal subjects at entry and 2 years after r and omization . Two years after r and omization oestradiol levels were 20 % ( 70 pmol l(-1 ) ) lower ( P = 0.04 ) and progesterone levels were 35 % ( 1.0 nmol l(-1 ) ) lower ( P = 0.004 ) and follicle-stimulating hormone ( FSH ) levels were 7 % ( 1 IU ) higher ( P = 0.38 ) in the intervention group than in the control group . The FSH-oestradiol ratio was 13 % higher in the intervention group ( P = 0.18 ) . Sample s analysed accounting for the timing of the blood sample in relation to the menstrual cycle showed that , in the intervention group , oestradiol and progesterone levels were lower and FSH levels higher in subjects with blood sample s taken more than 30 days after the last menstrual period . Because of the strong evidence linking ovarian hormonal activity to breast cancer risk , these results suggest that a low-fat high-carbohydrate diet may reduce risk of breast cancer by reducing exposure to ovarian hormones that are a stimulus to cell division in the breast OBJECTIVE Restriction of dietary fat and cholesterol are recommended for treating hyperlipidemia , but may alter vitamin or mineral intakes . We evaluated changes in nutrients of individuals taught the National Cholesterol Education Program ( NCEP ) Step II diet . METHODS Subjects participated in a r and omized controlled trial of the cholesterol-lowering effect of the NCEP Step II diet . Eligibility criteria included elevated fasting plasma LDL-cholesterol , no lipid-altering medications , and diet not already fat-modified . Subjects attended eight weekly dietitian-led classes . Four-day food records collected 6 months post-intervention were compared to baseline records . RESULTS Of 409 subjects with complete data , 123 met Step I and 166 met Step II diet criteria . Intakes of micronutrients associated with fruits and vegetables ( beta-carotene and vitamin A , vitamin C , folic acid , magnesium , and potassium ) increased on both diets . Patterns of decreased mean intake and /or fewer subjects consuming 2/3 Recommended Dietary Allowance were seen for calcium , vitamin E , and zinc . CONCLUSIONS NCEP Step I and II diets generally match or exceed unmodified diet for vitamin and mineral content . Premenopausal women do not appear to be at increased risk of low iron intake . Vitamin E intake decreases , although the significance is unknown in the context of lower fat intake and increased intake of other antioxidants . Diet counseling and material s should encourage sources of calcium for women , and zinc for both women and men BACKGROUND The " Mediterranean " diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease ( IHD ) , but no studies have evaluated the effect of this combination on endothelial function . We therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity . METHODS A total of 131 consecutive patients with documented IHD and a serum cholesterol level > or = 5 mmol/L ( 193 mg/dL ) were r and omized to receive Mediterranean dietary advice ( n = 68 ) or no specific dietary advice ( n = 63 ) . Endothelial function was assessed at baseline and after 12 months with noninvasive ultrasound scanning vessel-wall tracking of brachial artery flow-mediated vasodilatation ( FMD ) . All patients started statin treatment with Fluvastatin ( 40 mg once daily ) at baseline . RESULTS A total of 115 patients completed the study . At baseline , FMD was 4.30 % + /- 4.89 % in the control group versus 4.32 % + /- 6.15 % in the intervention group ( P = not significant ) . After 12 months of follow-up , FMD was significantly higher in the intervention group ( control group 5.72 % + /- 4.87 % vs intervention group 8.62 % + /- 6.60 % , P < .01 ) . This was accompanied by a larger intake of fatty fish and a significant decrease in triglyceride levels . In multivariate analysis , r and omization status was a significant predictor of FMD after adjustment for classic cardiovascular risk factors and vessel size ( P = .02 ; beta = -2.66 [ -4.91 ; -0.41 ] ) . CONCLUSION Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis , we set up a r and omised , controlled , end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infa rct ion . Another intervention group received diet and cholestyramine , to determine the effect of a greater reduction in circulating cholesterol concentrations . 90 men with coronary heart disease ( CHD ) , who had a mean ( SD ) plasma cholesterol of 7.23 ( 0.77 ) mmol/l were r and omised to receive usual care ( U , controls ) , dietary intervention ( D ) , or diet plus cholestyramine ( DC ) , with angiography at baseline and at 39 ( SD 3.5 ) months . Mean plasma cholesterol during the trial period was 6.93 ( U ) , 6.17 ( D ) , and 5.56 ( DC ) mmol/l . The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions ( U 46 % , D 15 % , DC 12 % ) , whereas the proportion who showed an increase in luminal diameter rose significantly ( U 4 % , D 38 % , DC 33 % ) . The mean absolute width of the coronary segments ( MAWS ) studied decreased by 0.201 mm in controls , increased by 0.003 mm in group D , and increased by 0.103 mm in group DC ( p less than 0.05 ) , with improvement also seen in the minimum width of segments , percentage diameter stenosis , and edge-irregularity index in intervention groups . The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period . Both interventions significantly reduced the frequency of total cardiovascular events . Dietary change alone retarded overall progression and increased overall regression of coronary artery disease , and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter . These findings support the use of a lipid-lowering diet , and if necessary of appropriate drug treatment , in men with CHD who have even mildly raised serum cholesterol concentrations The Polyp Prevention Trial ( PPT ) is a multicenter r and omized controlled trial examining the effect of a low-fat ( 20 % of total energy intake ) , high-fiber ( 18 g/1000 kcal ) , high-vegetable and -fruit ( 5 - 8 daily servings ) dietary pattern on the recurrence of adenomatous polyps of the large bowel , precursors of most colorectal malignancies . Eligibility criteria include one or more adenomas removed within 6 months of r and omization ; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy : age 35 years of more ; no history of colorectal cancer , inflammatory bowel disease , or large bowel resection ; and satisfactory completion of a food frequency question naire and 4-day food record . Of approximately 38,277 potential participants with one or more polyps recently resected , investigators at eight clinical centers r and omized 2,079 ( 5.4 % ; 1,037 in the intervention and 1,042 in the control arm ) between June 1991 and January 1994 , making the PPT the largest adenoma recurrence trial ever conducted . Of PPT participants , 35 % are women and 10 % are minorities . At study entry , participants averaged 61.4 years of age ; 14 % of them smoked , and 22 % used aspirin . At the baseline colonoscopy , 35 % of participants had two or more adenomas , and 29 % had at least one large ( > of = 1 cm ) adenoma . Demographic , behavioral , dietary , and clinical characteristics are comparable across the two study arms . Participants have repeat colonoscopies after 1 ( T(1 ) ) and 4 ( T(4 ) ) years of follow-up . The primary end point is adenoma recurrence ; secondary end points include number , size , location , and histology of adenomas . All resected lesions are review ed central ly by gastrointestinal pathologists . The trial provides 90 % power to detect a reduction of 24 % in the annual adenoma recurrence rate . The primary analytic period , on which sample size calculations were based is 3 years ( T(1 ) to T(4 ) ) , which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1 ) , given that at least 10 - 15 % of polyps may be missed at baseline . The final ( T(4 ) ) colonoscopies are expected to be completed in early 1998 Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK ) OBJECTIVE To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride ( TG ) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control . RESEARCH DESIGN AND METHODS In a parallel group design study , 30 subjects were r and omly assigned and completed one of the two eucaloric diets . Assessment s included : BMI , blood pressure , A1C , plasma lipids , and markers of oxidation , thrombosis , and inflammation . At 6 months , subjects were hospitalized for 24 h to measure plasma TG excursions . RESULTS There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 ( PAI-1 ) levels and weight gain in the lower-carbohydrate/higher – monounsaturated fat group . During the 24-h testing , the lower-carbohydrate/higher – monounsaturated fat group had a lower plasma TG profile . CONCLUSIONS A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control The objective of the present study was to determine the effects of a long-term moderate-fat diet ( 30 % energy from fat ) v. a low-fat one ( 20 % energy from fat ) on metabolic risks . The study was a r and omised , prospect i ve 14-month trial on overweight and obese patients ( eighty-nine overweight and obese men and women ) . The intervention was a moderate-fat diet ( 30 % energy ) or a low-fat diet ( 20 % energy ) . The main outcome measurements were change in body weight , waist circumference , LDL-cholesterol , HDL-cholesterol , total cholesterol , TAG , and systolic and diastolic blood pressure . Forty-five subjects on the moderate-fat diet and forty-four subjects on the low-fat one were studied . Characteristics of all r and omised participants were similar in both groups . After 7 months , the moderate- and low-fat diets had similar effects on cardiovascular risks . The moderate-fat diet was more successful after 14 months in reducing weight ( -5.0 ( SD 2.5 ) kg in the moderate-fat group v. -1.2 ( SD 1.1 ) kg in the low-fat one ; P < 0.0001 ) , waist circumference ( -5.5 ( SD 2.4 ) cm in the moderate-fat group v. - 2.3 ( SD 1.3 ) cm in the low-fat one ; P < 0.0001 ) , and other cardiovascular risk factors as well ( LDL , TAG , total cholesterol and systolic blood pressure ) . In conclusion , a moderate-fat energy-restricted diet in the long term might have more beneficial effects on weight maintenance and cardiovascular risk factors compared with a low-fat diet . Better dietary adherence with the moderate-fat diet may be the reason for its successful effects We evaluated dietary counselling by dietitians in hypercholesterolaemic hypertensives over 6 months . A total of 141 patients were r and omly assigned to intensive advice or usual care . Body weight fell significantly in the intervention group , but did not in the controls . There was a modest but significant fall in total cholesterol from 7.1 to 6.8 and 7.1 to 6.9 mmol/l in the diet and the control groups , respectively ( 4 and 3 % ) . A similar pattern emerged from the triglyceride measurements . Low-density lipoprotein fell in both groups , but only achieved significance ( P less than 0.05 ) in the intervention group . High-density lipoprotein did not change . There was a more marked change in cholesterol when serum levels during the study were compared with the previous annual review . These falls occurred after selection for the study but before r and om allocation to groups . They are unlikely to reflect regression to the mean as the lipids were stable for 2 or more years before the study , but may reflect spontaneous changes in diet after the patients were labelled hypercholesterolaemic . Dietary advice can lower total cholesterol but the magnitude of this decrease is small . Additional approaches are likely to be required to reduce plasma cholesterol to a normal range OBJECTIVE To assess the short-term ( 15-d ) and long-term ( 12-month ) effects of a school-based health and nutrition education intervention on diet , nutrition intake and BMI . DESIGN The 12-week teacher-implemented intervention in combination with seminars organized for parents was aim ed at improving children 's diet and nutrition knowledge . The intervention took place between September 2007 and January 2008 . The participants were r and omized to two study groups , the intervention group ( IG ) and control group ( CG ) , and were examined prior to the intervention on a variety of health knowledge , dietary , behavioural and anthropometric indices . The same measurements were collected 15 d and 1 year after the intervention . SETTING All high schools in Vyronas , a densely populated district of Athens , Greece . SUBJECTS The sample consisted of 191 students aged 12 - 13 years . RESULTS Twelve months after the intervention , the programme was effective in reducing various indices in the IG compared with baseline findings ( BMI : 23.3 ( sd 2.8 ) v. 24.0 ( sd 3.1 ) kg/m2 , P < 0.001 ; daily energy intake : 8112.4 ( sd 1412.4 ) v. 8503.3 ( sd 1419.3 ) kJ/d , P < 0.001 ; total fat intake : 31.3 ( sd 4.4 ) v. 35.4 ( sd 4.7 ) % of daily energy , P < 0.001 ) . Except for BMI , decreases in the aforementioned indices were also observed 15 d after the intervention . In addition , students of the IG reduced their weekly consumption of red meat and non-home-made meals and increased their frequency of fruit and breakfast cereal consumption . CONCLUSIONS The beneficial effects of this nutrition education intervention among adolescents may highlight the potential of such programmes in the prevention of obesity The Polyp Prevention Trial ( PPT ) is a multicenter r and omized controlled trial to evaluate whether a low-fat , high-dietary fiber , high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel . Men and women who had one or more adenomas removed recently were r and omized into either the intervention ( n = 1037 ) or control ( n = 1042 ) arms . Food frequency question naire data indicate that PPT participants at the beginning of the trial consumed 36.8 % of total energy from fat , 9.7 g of dietary fiber/1000 kcal , and 3.8 daily servings of fruits and vegetables . Baseline dietary characteristics , including intake of fat , fiber , and fruits and vegetables , as well as other macro- and micronutrients , were similar in the two study groups . The intervention participants receive extensive dietary and behavioral counseling to achieve the PPT dietary goals of 20 % of total energy from fat , 18 g/1000 kcal of dietary fiber , and 5 - 8 daily servings ( depending on total caloric intake ) of fruits and vegetables . Control participants do not receive such counseling and are expected to continue their usual intake . Dietary intake in both groups is mentioned annually using a 4-day food record ( also completed at 6 months by intervention participants only ) and a food frequency question naire , with a 10 % r and om sample of participants completing an annual unscheduled 24-h telephone recall . Blood specimens are drawn and analyzed annually for lipids and carotenoids . This article provides details on the rationale and design of the PPT dietary intervention program and describes the participant baseline dietary intake data characteristics Dietary patterns that involve a decrease in fat and an increase in fruit and vegetable ( FV ) intake have been suggested to decrease cancer risks . In this study , intervention methods to selectively modify dietary fat and /or FV intakes were developed . Compliance to the diets and the effects on body weight are shown , because both of these dietary changes can impact on and be confounded by changes in energy intake . A total of 122 women with a family history of breast cancer were r and omized onto one of four diets for 12 mo . Counseling methods were devised to increase amount and variety of FV consumed with or without a decrease in fat intake using modified exchange list diets . Women on the low-fat and combination low-fat/high-FV diet arms decreased their fat intakes to ~16 % of energy . Women on the high-FV and the combination low-fat/high-FV diet arms increased FV intakes to ~11 servings/day . Despite counseling efforts to maintain baseline energy intakes , mean body weight increased significantly by 6 pounds in women in the high-FV diet arm and decreased significantly by 5 pounds in women in the low-fat diet arm . Percent body fat also was increased in the high-FV diet arm and decreased in the low-fat diet arm . Body weight and percent body fat in the combination diet arm did not change significantly . Control of energy intake , therefore , appears to have been achieved only when the addition of FV to the diet was balanced by a decrease in fat intake and both dietary components were enumerated daily . Maintenance of energy intake , therefore , did not appear to be attained intrinsically when individuals were counseled to make changes in the composition of their diets OBJECTIVE The Women 's Health Trial : Feasibility Study in Minority Population s ( WHT : FSMP ) documented that a low-fat diet was associated with a reduced fat intake in older women of diverse ethnic background s. The purpose of the current study was to examine the effect of the low-fat diet on anthropometric and biochemical variables . DESIGN R and omized clinical trial in 2,208 postmenopausal women , 50 to 79 years of age . RESULTS The decrease in fat intake correlated directly with a decrease in body weight ( r=.22 , P<.001 ) . After 6 months , the intervention group had an average weight loss of 1.8 kg . Body mass index decreased 0.7 kg/m2 . Waist circumference decreased 1.8 cm . All of these changes were statistically significant , compared to changes in the control group ( P<.01 ) . Changes in systolic ( -3.1 mm Hg ) and diastolic ( -1.1 mm Hg ) blood pressures ( BP ) occurred in the intervention group . The decrease in systolic BP reached statistical significance ( P=.02 ) , relative to the control group . Decreases in plasma glucose were small ( -0.2 mmol/L ) in the intervention group , although there was a trend for difference from the control group ( P=.11 ) . Decreases in serum insulin levels were small ( -0.5 microIU/mL ) in the intervention group , although there was , again , a trend for difference from the control group . CONCLUSIONS In older White , Black , and Hispanic women , a long-term low-fat dietary intervention was accompanied by modest , but statistically significant , decreases in body weight and anthropometric indices , without any particular attempt being made to reduce calories . Changes in glucose and insulin were small . The long-term biological significance of the glucose and insulin changes is unknown UNLABELLED In a 3-month intervention study 70 women ( 40 < age < 60 ; 24 < BMI < 29 ) , r and omized into two groups , were supplied ad libitum and free of charge with 1 ) customary fat-reduced foods ( D group ) or 2 ) products with normal fat content ( K group ) . After 6 months without any contact to the volunteers food intake and body weight were controlled . RESULTS During the intervention period fat intake ( by 22 g/d ) and total energy intake ( by 266 kcal/d ) of the volunteers in the D group were significantly lower than in the K group . Fat reduction was not accompanied by a compensative increase in the intake of other nutrients . The weight loss was significant in the D group ( 1.5 kg ) and not significant in the K group ( 0.7 kg ) . Between the two groups the difference in weight reduction was not significant . In the follow-up a lowered fat and energy intake had been voluntarily retained in the D group and adopted by most of the individuals in the K group . CONCLUSION The consumption of low-fat products lowers the energy and fat intake and may be useful for a long-term weight control and health support Effects of dietary intervention on food choice were studied in 240 women aged 50 - 65 years who had been operated for a stage I-II breast cancer . Following surgery , the women participated in a dietary history interview and were then r and omized to one of two groups . The intervention group ( n = 121 ) received individual dietary counselling aim ed at reducing dietary fat intake to 20 - 25 % energy ( E% ) , whereas no dietary advice was given to women in the control group ( n = 119 ) . For the 52 % of the women in the intervention group that completed the study the total fat intake decreased from 36 to 23 E% ( P less than or equal to 0.01 ) and from 37 to 34 E% ( P less than or equal to 0.01 ) for the control group . There were significant reductions in the intake of table fat , high-fat milk products , pork and sausages ( containing greater than 11 % fat ) , eggs , rice , pasta , cakes and chocolate for the intervention group . Concurrently the intake of vegetables , fruits , potatoes , bread , cereals , low-fat milk products , low-fat meat , sausages and fish increased significantly . For the control group there was a significant decrease in the consumption of total milk products , total meats , rice , pasta , cakes , and butter intake while the consumption of vegetables , fruits , cereals and fish increased ( P less than or equal to 0.01 ) . Reduction of high-fat foods and increases of carbohydrate-rich foods were more pronounced for the intervention group than for the control group . Formal education influenced dietary changes , and dietary counselling should therefore ideally be adapted to education level . This study showed that dietary counselling can bring about significant changes in consumption of high-fat foods for at least a 2-year period for women operated for breast cancer Summary We conducted a 2-year prospect i ve r and omised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 ( insulin-dependent ) diabetic patients with elevated urinary albumin excretion ( overnight urinary albumin excretion rate between 10 and 200 μg/min ) . Thirty-eight patients were r and omly assigned to increase dietary polyunsaturated : saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products ( n=18 , two dropouts , analysis was performed in n=16 ) or to continue their usual diet ( n=20 ) . The total fat and protein content of the diet was unaltered . Clinical characteristics , albuminuria , blood pressure , glomerular filtration rate , metabolic control and dietary composition were similar in the two groups at baseline . In the high linoleic acid diet group , linoleic intake rose from 7±4 to 11±2 energy % and polyunsaturated : saturated fatty acids ratio rose from 0.60±0.28 to 0.96±0.16 ( p<0.001 compared to usual diet group ) . The median increase albuminuria was 58 % ( 95 % confidence interval , 13 to 109 ) during the first year ( p<0.02 ) and 55 % ( 95 % confidence interval , 11 to 127 ) ( p<0.01 ) during the second year . Glomerular filtration rate remained unaltered and filtration fraction tended to rise ( p<0.05 compared to usual diet group ) . In the usual diet group , albuminuria did not significantly increase by 16 % ( 95 % confidence interval , -17 to 38 ) and glomerular filtration rate declined during the second year . Blood pressure tended to rise similarly in both groups . Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate . Low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group ( p<0.05 ) . High density lipoprotein cholesterol declined in both groups ( p<0.05 ) . It is concluded that a linoleic-acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in Type 1 diabetic patients with elevated urinary albumin excretion To study the impact of dietary intervention on the plasma total and high density lipoprotein cholesterol ( HDL cholesterol ) levels in hypercholesterolemic men , the authors selected 80 male participants in a monitoring risk factor project carried out in Amsterdam , The Netherl and s. These men had plasma total cholesterol levels of between 6.5 and 10.0 mmol/liter ( between 251 and 387 mg/dl ) and were r and omly assigned to either the intervention ( n = 39 ) or the control ( n = 41 ) group . At the start of the intervention period , after 5 weeks , and after 26 weeks , both the intervention and the control groups were examined . This examination consisted of a measurement of height , weight , plasma total and HDL cholesterol , and a dietary interview . The intervention program consisted of a personalized dietary advice to the respondent , based on the report of the Netherl and s Nutrition Council . The study took place between September 1987 and November 1988 . Because of this intervention program , the plasma total and HDL cholesterol levels decreased . The difference in change in plasma total cholesterol between the intervention and control groups was 0.47 mmol/liter ( 18 mg/dl ) after 5 weeks and 0.30 mmol/liter ( 12 mg/dl ) after 26 weeks . For HDL cholesterol , a significant difference in change after 5 weeks disappeared after 26 weeks . The public health implication s of the decrease in plasma total cholesterol are discussed Summary Type 2 ( insulin independent ) diabetic women were r and omly allocated to receive advice for low fat diets or low carbohydrate diets . By 24 h weighed dietary intakes before and after a mean interval of six months , patients in the low fat group had reduced their fat intake from 41 % to 31 % of total energy , while carbohydrate percentage of total energy intake increased from 38 % to 46 % . Percentage energy intake from fat and carbohydrate in the control group remained unchanged . Body weight fell in both groups , especially for patients in the low fat group who were obese ( weight/height2 ⩾ 28 kg/m2 ) . Mean plasma glucose , HbA1 , and triglycerides were unchanged . Mean plasma total cholesterol fell significantly in the low fat group compared with the controls ( p < 0.001 ) , but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups . Thus , adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol OBJECTIVE To determine the effectiveness of an intensive dietary intervention on diet and body mass in women with breast cancer . DESIGN R and omized clinical trial . SUBJECTS 172 women aged 20 to 65 years with stage I or II breast cancer . INTERVENTION A 15-session , mainly group-based and dietitian-led nutrition education program ( NEP ) was compared to a mindfulness-based stress reduction clinic program ( SRC ) ; or usual supportive care ( UC ) . MAIN OUTCOME MEASURES Dietary fat , complex carbohydrates , fiber , and body mass were measured . STATISTICAL ANALYSIS In addition to descriptive statistics , analysis of variance was conducted to test for differences according to intervention group . RESULTS Of the 157 women with complete dietary data at baseline , 149 had complete data immediately postintervention ( at 4 months ) and 146 had complete data at 1 year . Women r and omized to NEP ( n = 50 ) experienced a large reduction in fat consumption ( 5.8 % of energy as fat ) at 4 months and much of this reduction was preserved at 1 year ( 4.1 % of energy ) ( both P < .0002 ) vs no change in either SRC ( n = 51 ) or UC ( n = 56 ) . A 1.3-kg reduction in body mass was evident at 4 months in the NEP group ( P = .003 ) vs no change in the SRC and UC groups . Women who had higher-than-average expectations of a beneficial effect of the intervention experienced larger changes . APPLICATIONS Dietitians ' use of group nutrition interventions appear to be warranted . Increasing their effectiveness and maintaining high levels of adherence may require additional support , including the involvement of significant others , periodic individual meetings , or group booster sessions CONTEXT Evidence is lacking that a dietary pattern high in vegetables , fruit , and fiber and low in total fat can influence breast cancer recurrence or survival . OBJECTIVE To assess whether a major increase in vegetable , fruit , and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer . DESIGN , SETTING , AND PARTICIPANTS Multi-institutional r and omized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis . Women were enrolled between 1995 and 2000 and followed up through June 1 , 2006 . INTERVENTION The intervention group ( n = 1537 ) was r and omly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice ; 3 fruit servings ; 30 g of fiber ; and 15 % to 20 % of energy intake from fat . The comparison group ( n = 1551 ) was provided with print material s describing the " 5-A-Day " dietary guidelines . MAIN OUTCOME MEASURES Invasive breast cancer event ( recurrence or new primary ) or death from any cause . RESULTS From comparable dietary patterns at baseline , a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years : servings of vegetables , + 65 % ; fruit , + 25 % ; fiber , + 30 % , and energy intake from fat , -13 % . Plasma carotenoid concentrations vali date d changes in fruit and vegetable intake . Throughout the study , women in both groups received similar clinical care . Over the mean 7.3-year follow-up , 256 women in the intervention group ( 16.7 % ) vs 262 in the comparison group ( 16.9 % ) experienced an invasive breast cancer event ( adjusted hazard ratio , 0.96 ; 95 % confidence interval , 0.80 - 1.14 ; P = .63 ) , and 155 intervention group women ( 10.1 % ) vs 160 comparison group women ( 10.3 % ) died ( adjusted hazard ratio , 0.91 ; 95 % confidence interval , 0.72 - 1.15 ; P = .43 ) . No significant interactions were observed between diet group and baseline demographics , characteristics of the original tumor , baseline dietary pattern , or breast cancer treatment . CONCLUSION Among survivors of early stage breast cancer , adoption of a diet that was very high in vegetables , fruit , and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00003787 BACKGROUND Guidelines established by the National Cholesterol Education Program ( NCEP ) promote exercise and weight loss for the treatment of abnormal lipoprotein levels . Little is known , however , about the effects of exercise or the NCEP diet , which is moderately low in fat and cholesterol , in persons with lipoprotein levels that place them at high risk for coronary heart disease . METHODS We studied plasma lipoprotein levels in 180 postmenopausal women , 45 through 64 years of age , and 197 men , 30 through 64 years of age , who had low high-density lipoprotein ( HDL ) cholesterol levels ( < or = 59 mg per deciliter in women and < or = 44 mg per deciliter in men ) and moderately elevated levels of low-density lipoprotein ( LDL ) cholesterol ( > 125 mg per deciliter but < 210 mg per deciliter in women and > 125 mg per deciliter but < 190 mg per deciliter in men ) . The subjects were r and omly assigned to aerobic exercise , the NCEP Step 2 diet , or diet plus exercise , or to a control group , which received no intervention . RESULTS Dietary intake of fat and cholesterol decreased during the one-year study ( P<0.001 ) , as did body weight , in women and men in either the diet group or the diet-plus-exercise group , as compared with the controls ( P<0.001 ) and the exercise group ( P<0.05 ) , in which dietary intake and body weight were unchanged . Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups , for subjects of either sex . The serum level of LDL cholesterol was significantly reduced among women ( a decrease of 14.5+/-22.2 mg per deciliter ) and men ( a decrease of 20.0+/-17.3 mg per deciliter ) in the diet-plus-exercise group , as compared with the control group ( women had a decrease of 2.5+/-16.6 mg per deciliter , P<0.05 ; men had a decrease of 4.6+/-21.1 mg per deciliter , P<0.001 ) . The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group ( 3.6+/-18.8 mg per deciliter , P<0.001 ) . In contrast , changes in LDL cholesterol levels were not significant among the women ( a decrease of 7.3+/-18.9 mg per deciliter ) or the men ( 10.8+/-18.8 mg per deciliter ) in the diet group , as compared with the controls . CONCLUSIONS The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise . This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels In 1982 we started a series of pilot studies to examine the feasibility of dietary intervention with a low-fat , high-carbohydrate diet in women with extensive mammographic densities . The purpose of the present paper is to examine the long-term effects of participation in these studies by assessing nutrient intake and other variables several years after active participation had stopped . Two hundred sixteen women were eligible for the follow-up study and were invited to attend and interview with a dietician . Data were collected by food frequency question naire from 157 subjects ( 73 % ) , and blood was obtained from 115 subjects . Total energy intake was slightly lower in the intervention group . Total fat and percent energy from fat were significantly lower in the intervention group . The intake of all types of fat ( saturated fat , linoleic acid , and oleic acid ) and dietary cholesterol was lower in the in the intervention group ; however , the polyunsaturated/saturated fat ratio did not differ between the groups . Total cholesterol and apoprotein B levels were lower in the intervention group compared to the control group . Follicle-stimulating hormone was 29 % higher in postmenopausal members of the intervention group than in controls , but there was no difference in levels of estradiol . A total of 19 women enrolled in pilot studies had developed breast cancer , 5.7 times the number expected , confirming that the selection of women with extensive mammographic densities does identify a high-risk group . These data suggest that even quite short periods of intensive dietary counselling may have prolonged effects on diet , and that once subjects have adopted new dietary habits , the habits may persist even in the absence of continued counselling The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products . However , no consensus exists on the effectivity of reduced fat products to decrease energy intake . The studies that have investigated this topic have included small numbers of subjects , studied under laboratory conditions and over a relatively short period of time . Therefore , we have executed a long-term study in which volunteers had free access to both reduced fat , commercially available products in the laboratory as well as to products obtained from regular shops . We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol , haemostasis variables , antioxidants and parameters of the immune system . The study was a multicentre parallel comparison trial of six months ( so-called MSFAT- study ) . 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such . Two months before the start of the study , a 1 month adaptation period was executed to optimize the experimental procedures . Food intake was recorded before the start of the adaptation period and 2 - 4 weeks , 3 months and 6 months after the start of the study . Blood sample s were taken before , after 2 , 4 and 6 months of the study . In addition , a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers . 220 volunteers completed the study . The reduced fat group consumed on average 46 % less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study . The palatability of the reduced fat and full-fat products was similar and as expected , the perceived fattiness of the full-fat products was higher than that of the reduced fat products . No effects were found on blood levels of cholesterol , haemostasis variables , parameters of antioxidant status and immune system characteristics . In conclusion , the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions . The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels , antioxidant status , haemostasis factors and the body 's immune system A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI The beFIT study tested whether teaching the NCEP step II diet ( < 30 % of calories from total fat and < 7 % from saturated fat ) is an effective therapy in hypercholesterolemic women and men with or without elevated triglycerides after 6 months . Hypercholesterolemic subjects had two LDL cholesterol measurements above the age- and sex-specific 75th percentile , and combined hyperlipidemic subjects additionally had similarly elevated triglyceride . Subjects were r and omized to receive dietary intervention ( eight weekly classes ) immediately or 6 months later . Follow-up visits were quarterly , with lipid measurements and 4-day food records . Subjects r and omized to delayed intervention did not report diet changes or experience lipid changes ; the immediate intervention group significantly reduced fat and cholesterol intake , result ing in significant LDL cholesterol lowering . Six months after diet instruction , 178 women and 231 men reported total and saturated fat intakes of approximately 25 % and 7.5 % kcal LDL cholesterol was significantly reduced in women ( 7.6 % and 8.1 % ) and men ( 8.8 % and 8.1 % ) with hypercholesterolemia and combined hyperlipidemia , respectively , but was not different by sex or lipid disorder . C and i date s for drug therapy were reduced from between 27 % and 37 % to 20 % . HDL cholesterol was significantly decreased in women ( -6.4 % and -4.7 % ) but not in men ( -1.3 % and -2.7 % ) . The 6.4 % reduction in hypercholesterolemic women was significantly different from that of men . The significance of the HDL cholesterol reduction in women is unknown . LDL cholesterol response was similar between women and men and between hypercholesterolemic and combined hyperlipidemic subjects . LDL cholesterol lowering by diet can significantly reduce the number of hyperlipidemic persons requiring drug therapy CONTEXT Weight loss , sodium reduction , increased physical activity , and limited alcohol intake are established recommendations that reduce blood pressure ( BP ) . The Dietary Approaches to Stop Hypertension ( DASH ) diet also lowers BP . To date , no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations . OBJECTIVE To determine the effect on BP of 2 multicomponent , behavioral interventions . DESIGN , SETTING , AND PARTICIPANTS R and omized trial with enrollment at 4 clinical centers ( January 2000-June 2001 ) among 810 adults ( mean [ SD ] age , 50 [ 8.9 ] years ; 62 % women ; 34 % African American ) with above-optimal BP , including stage 1 hypertension ( 120 - 159 mm Hg systolic and 80 - 95 mm Hg diastolic ) , and who were not taking antihypertensive medications . INTERVENTION Participants were r and omized to one of 3 intervention groups : ( 1 ) " established , " a behavioral intervention that implemented established recommendations ( n = 268 ) ; ( 2 ) " established plus DASH,"which also implemented the DASH diet ( n = 269 ) ; and ( 3 ) an " advice only " comparison group ( n = 273 ) . MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months . RESULTS Both behavioral interventions significantly reduced weight , improved fitness , and lowered sodium intake . The established plus DASH intervention also increased fruit , vegetable , and dairy intake . Across the groups , gradients in BP and hypertensive status were evident . After subtracting change in advice only , the mean net reduction in systolic BP was 3.7 mm Hg ( P<.001 ) in the established group and 4.3 mm Hg ( P<.001 ) in the established plus DASH group ; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg ( P = .43 ) . Compared with the baseline hypertension prevalence of 38 % , the prevalence at 6 months was 26 % in the advice only group , 17 % in the established group ( P = .01 compared with the advice only group ) , and 12 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .12 compared with the established group ) . The prevalence of optimal BP ( < 120 mm Hg systolic and < 80 mm Hg diastolic ) was 19 % in the advice only group , 30 % in the established group ( P = .005 compared with the advice only group ) , and 35 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .24 compared with the established group ) . CONCLUSION Individuals with above-optimal BP , including stage 1 hypertension , can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk Summary To evaluate the feasibility of using a low-fat diet ( i.e. 20–25 % of energy ( E% ) as fat ) as a component of adjuvant therapy for breast cancer patients , 240 females aged 50–65 years and operated for a stage I-II breast cancer were entered into a r and omized study . The intervention group ( n = 121 ) was to reduce dietary fat intake to 20–25 E% and to increase the intake of carbohydrates . Dietary counselling complemented other adjuvant treatments and the patients were followed for two years . No dietary advice was given to patients in the control group ( n = 119).There was no significant difference between the groups in terms of base-line nutrient intake except for higher energy intake in the control group ( p < 0.05 ) . Only 52 % of the patients in the intervention group followed through with the dietary regimen for two years , and 89 % of the patients in the control group had a two-year follow-up . Energy intake decreased in both groups after two years , and the difference between the two groups remained ( p < 0.01 ) . Total fat intake decreased from 36.2 E% to 22.2 E% after one year in the intervention group and remained at that level after two years . Total fat intake in the control group decreased by 3.6 E% after two years . The low compliance raises concern about the protocol design . The study nevertheless indicates that a long-term reduction of dietary fat intake can be implemented in breast cancer patients Effects of dietary intervention on dietary habits and nutrient levels were studied in 240 women aged 50 - 65 years who had been operated for a stage I-II breast cancer . Following surgery the women who had participated in a dietary history interview were r and omly assigned to one of two groups . The intervention group ( n = 121 ) received individual dietary counselling aim ed at reducing dietary fat intake to 20 - 25 per cent of energy ( E per cent ) while increasing intake of carbohydrates . No dietary advice was given to women assigned to the control group ( n = 119 ) . There was no significant difference between the groups in terms of base-line nutrient intake except for a higher energy intake in the control group ( P less than 0.05 ) . Sixty-three ( 52 per cent ) of the women in the intervention group and 106 ( 89 per cent ) of the women in the control group completed the 2-year follow-up . Energy intake decreased after 2 years in both groups and the difference between the groups remained ( P less than 0.01 ) . Total fat intake decreased in the intervention group by 12.9 - 23.3 E per cent after 2 years and by 3.1 E per cent in the control group . The intake of carbohydrates increased from 46.2 to 57.2 E per cent in the intervention group and from 46.2 to 48.9 E per cent in the control group . The study shows that dietary habits and intake of nutrients can be altered through dietary counselling to breast cancer patients , and that such changes are long lasting PURPOSE To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer . PATIENTS AND METHODS Two hundred ninety postmenopausal women with localized ( stage I to IIIa ) breast cancer receiving conventional systemic therapy provided informed consent and were r and omized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling . RESULTS Significantly reduced ( P < .001 ) fat intake ( in terms of percent calories derived from fat ) was observed in the intervention group versus the control group at 3 months ( 20.3 % + /- 2.4 % v 31.5 % + /- 2.6 % , mean + /- SD , respectively ) and maintained throughout 24 months of observation . The 50 % reduction in daily fat-gram intake ( from 66 + /- 23 to 33 + /- 14 g , P < .001 ) seen at 6 months was associated with reduced saturated fat , monounsaturated fat , polyunsaturated fat , and linoleic acid ( P < .001 ) . Significantly lower body weight was also seen in intervention compared with control patients at all observation periods , result ing in a 3.3-kg weight difference 18 months after r and omization ( P < .001 ) . CONCLUSION Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer . This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients |
434 | 22,397,851 | The dry-mouth rates were statistically significantly higher with anticholinergics , with no difference in withdrawals because of adverse events .
There was no statistically significant difference in any of the outcomes between oxybutynin and other anticholinergics or among different doses and preparations of anticholinergic drugs .
CONCLUSIONS Compared with placebo , anticholinergic treatment in patients with NDO is associated with better patient-reported cure/improvement and significant reduction of maximum detrusor pressure ; however , there is a higher incidence of adverse events .
None of the anticholinergic drugs or different dosages assessed in this review was superior to another | CONTEXT There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug , if any , for the treatment of adult neurogenic detrusor overactivity ( NDO ) .
OBJECTIVE Review the current evidence on the efficacy , safety , and tolerability of anticholinergic drugs in the treatment of adult NDO . | In a multicentre placebo-controlled double-blind study 61 patients with spinal cord injuries and detrusor hyperreflexia were treated : 20 mg trospium chloride was given twice daily over a period of 3 weeks . Pre- and posttreatment urodynamic measurements demonstrated large improvements in maximum cystometric capacity ( mean = 138.1 ml ) , decreased maximum detrusor pressure ( mean = -37.8 cm H2O ) and an increase in compliance ( mean = 12.1 ml/cm H2O ) in the treatment group . Urodynamic parameters in the placebo group remained substantially unchanged . Comparisons between the two groups revealed highly significant differences for these parameters ( all , p less than 0.001 ) . No effect on maximum flow rate and residual urine was detected in either group . The incidence of spontaneously reported side-effects was extremely low and comparable for both groups Aims of the study : The aim of this double-blind , r and omised , prospect i ve , multicentre trial was to evaluate the efficacy of propiverine in patients suffering from detrusor hyperreflexia caused by spinal cord injury in comparison to placebo . Study design : The treatment period of 14 days comprised visits at baseline ( V1 ) and after 14 days treatment ( V2 ) . Fifteen mg propiverine t.i.d . or placebo t.i.d . were administered as medication . The following efficacy parameters were adopted : the urodynamic parameters maximal cystometric bladder capacity , bladder volume on onset of the first as well as duration and amplitude of the maximum detrusor contraction , bladder compliance and residual urine , and subjective assessment of efficacy by physicians . For the evaluation of the safety of propiverine the incidence rate of adverse events by directly question ing as well as laboratory parameters were investigated . For biometrical evaluation t-test for independent groups was applied . Results : One hundred and thirteen patients were investigated . The maximal cystometric bladder capacity increased significantly in the propiverine group , on average by 104 ml ( V1 : 262±132 ml . V2 : 366±143 ml , P<0.001 ) . The changes in bladder capacity during the first contraction and the maximum detrusor contraction in the verum group were both statistically significant . The bladder compliance documented a more pronounced increase under propiverine in comparison to placebo . Residual urine increased by 37±71 ml in the propiverine group , significantly more than in the placebo group ( P=0.01 ) . Sixty-three per cent of the patients expressed subjectively an improvement under propiverine in comparison with 23 % of the placebo group . Expected anticholinergic adverse events occurred : dryness of the mouth ( 37 % in the verum and 8 % in the placebo group ) , accommodation disorders ( 28 % and 2 % respectively ) . Nausea , constipation , headache , dizziness , tiredness and palpitations were reported in almost comparable incidence rates between 3 and 13 % in both treatment groups . Eight drop-outs were registered in the propiverine group ( five due to adverse events ) and three in the placebo group ( one due to adverse events ) . The laboratory parameters revealed no changes . Conclusion : Propiverine proved its efficacy in detrusor hyperreflexia with regard to the urodynamic parameters of the maximal cystometric bladder capacity and detrusor contractility . Anticholinergic adverse events such as dryness of the mouth and accommodation disorders were considered being tolerable . The increase in residual urine reflects the therapeutically desired effect of detrusor relaxation because the majority of patients normally practise intermittent catheterisation for bladder emptying Abstract Objective : To compare tolterodine with oxybutynin and placebo in people with neuragenie detrusor overactivity . Design : Prospect i ve , r and omized , double-blind , crossover trial plus open-label comparative stage . Participants : Ten participants with neuragenie detrusor overactivity due to spinal cord injury or multiple sclerosis who usedintermittent catheterization . Methods : Bladder capacity on cystometrogram , a 10-day record of catheterization volumes , number of incontinent episodes perday , and perceived dry mouth using a visual analog scale ( VAS ) were measured for the following : ( a ) a blinded comparison : tolterodine , 2 mg twice daily , vs placebo , twice daily ; and ( b ) an unblinded comparison : oxybutynin vs tolterodine , each atself-selected doses ( SSDs ) . Results : Tolterodine , 2 mg twice daily , was superior to placebo in enhancing catheterization volumes ( P<0.0005 ) and reducingincontinence ( P<0.001 ) , but was comparable with placebo in cystometric bladder capacity . Efficacy of tolterodine SSD wascomparable with oxybutynin SSD with regard to catheterization volumes , degree of incontinence , and cystometric bladder capacity . The side effect profile ( dry mouth ) was comparable between tolterodine , 2 mg twice daily , and placebo , but differed significantlywhen comparing tolterodine SSD with oxybutynin SSD ( P<0.05 ) . Conclusion : T olterodine , when used at SSDs , is comparable with oxybutynin at SSDs in enhancing bladder volume and improvingcontinence , but with less dry mouth . T olterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladdervolumes compared with placebo , and without significant dry mouth . Larger doses of tolterodine may be needed to achieve best effectin this population , but further studies are required Hyperreflexia is the most common urological finding in patients with multiple sclerosis . A prospect i ve r and omized study was done to compare the effectiveness of 2 commonly used drugs , oxybutynin and propantheline . Of the 34 patients entered into the trial 19 were treated with oxybutynin and 15 with propantheline . The urological symptoms ( frequency , nocturia , hesitancy , urgency and urge incontinence ) were grade d according to severity from 0 to 3 . Patients with urinary infection were excluded . Urodynamic examination , consisting of cystometrography and electromyography , was performed in all patients before treatment . Both groups of patients had comparable neurological , urological and urodynamic status before treatment . In 4 patients ( 21 per cent ) treated with oxybutynin and in 4 ( 27 per cent ) treated with propantheline side effects were so severe that the treatment had to be discontinued . Symptomatic response to oxybutynin was good in 10 patients ( 67 per cent ) , fair in 2 ( 13 per cent ) and poor in 3 ( 20 per cent ) . Propantheline produced good symptomatic results in 4 patients ( 36 per cent ) , fair in 1 ( 9 per cent ) and poor in 6 ( 55 per cent ) . The mean increase in maximum cystometric capacity on cystometrography was significantly larger in the oxybutynin group than in the propantheline group ( 144 + /- 115 versus 35 + /- 101 ) . Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis PURPOSE About 15 % to 20 % of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens , frequently because of unpleasant side effects . Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond . MATERIAL S AND METHODS A select group of 10 adults with detrusor hyperreflexia unresponsive to st and ard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg . oxybutynin orally , or 5 mg . oxybutynin in 100 ml . intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current . Each treatment ( plus oral placebo and 2 intravesical controls ) was associated with an 8-hour , full urodynamic monitoring session , and periodic blood and bladder content sampling . RESULTS There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin . Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin . Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin . Area under the curve for intravesical passive diffusion were 709 ng . per 8 hours versus oral 1,485 ( p < 0.05 ) versus intravesical electromotive 2,781 ( p < 0.001 ) . Bladder content sample s confirmed oxybutynin absorption . Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients . There were no side effects with intravesical passive diffusion or electromotive administrations . CONCLUSIONS Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration Study design : Double-blind , r and omised , multicentre study . Objectives : Efficacy and tolerability of propiverine extended-release ( ER ) compared with immediate-release ( IR ) were evaluated in patients with proven neurogenic detrusor overactivity ( NDO ) . Setting : Six Spinal Cord Injury Units located in Austria , Germany and Romania . Methods : Propiverine ER 45 mg s.i.d . or IR 15 mg t.i.d . were administered in patients with proven NDO . Outcomes were assessed at baseline ( V1 ) , and after 21 days of treatment ( V2 ) : Reflex volume served as primary , leak point volume and maximum detrusor pressure as secondary efficacy outcomes , treatment-related adverse events as tolerability outcomes . Results : Sixty-six patients with proven NDO were enrolled . Reflex volume ( ml ) increased significantly in the IR ( V1 : 100.9 , V2 : 202.9 ) and in the ER ( V1 : 89.8 , V2 : 180.3 ) group , no significant intergroup difference . Leak point volume increased , and maximum detrusor pressure decreased significantly in both groups , no significant intergroup differences . The percentage of patients presenting with incontinence was reduced by 14 % in the IR and by 39 % in the ER group , the difference is significant . Treatment-related adverse events manifested in 42 and 36 % following propiverine IR and ER , respectively . Conclusion : The urodynamic efficacy outcomes demonstrated both galenic formulations to be equieffective . However , following propiverine ER 45 mg s.i.d . higher continence rates compared with propiverine IR 15 mg t.i.d . were achieved , possibly indicative of more balanced plasma-levels . A slight tendency for superior tolerability outcomes of propiverine ER compared with IR was demonstrated . Sponsorship : The study was sponsored by an unrestricted educational grant of APOGEPHA Arzneimittel GmbH , Dresden , Germany Abstract Objective : This study evaluated the effects and tolerability of extended-release oxybutynin chloride on the frequency of voiding and catheterization and urodynamic capacity in spinal cord injury ( SCI ) patients with defined detrusor hyperreflexia . Methods : This was a 1 2-week , prospect i ve , dose-titration study of extended-release oxybutynin ( oxybutynin XL ) . SCI patients with urodynamically defined detrusor hyperreflexia were recruited for this study . Following a 7 -day washout period , patients were evaluated via video-urodynamic study and then treatment was initiated at a dosage of 1 0 mg per day . Dosage was increased in weekly intervals to a maximum of 30 mg per day . Micturation frequency diaries and urodynamics were completed at baseline and repeated at week 1 2 . Tolerability information was collected at each follow-up visit . Results : Ten patients ( mean age = 49 years ) with complete or incomplete SCI were enrolled . Participants reported clinical improvement ( decreased urinary frequency and fewer incontinence episodes ) with oxybutynin therapy following titration to 30 mg per day . All patients chose a final effective dosage of greater than 1 0 mg , with 4 patients taking the maximum of 3 0 mg per day . Mean cystometric bladder capacity increased from 2 7 4 mL to 3 80 mL ( P = 0.008 ) . No patient experienced serious adverse events during the 12-week study . Conclusion : Oxybutynin XL is safe and effective in patients with detrusor hyperreflexia secondary to SCI . The onset of clinical efficacy occurs within 1 week , and daily dosages up to 30 mg are well tole rated Objective To compare the efficacy of a controlled‐release ( CR ) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper‐reflexia whose symptoms were stabilized on conventional oral oxybutynin tablets INTRODUCTION AND OBJECTIVES The dosage of the antimuscarinic drugs : Tolterodine ER or Trospium was increased to a higher-than-recommended dosage in patients where the manufacturer 's recommended dosage had failed . All patients were suffering from neurogenic detrusor overactivity incontinence . Tolerability and success were evaluated in the present study . MATERIAL S AND METHODS Twenty-one patients with neurogenic detrusor overactivity were evaluated : 17 with spinal cord injury , 3 with multiple sclerosis , and 1 with a meningomyelocele . All patients catheterized themselves or were catheterized . If neurogenic detrusor overactivity continued and the medication was well tolerated , the dosage was doubled to either 8 mg of Tolterodine ER [ 2 x 4 mg ( n = 11 ) ] or 90 mg of Trospium [ 3 x 30 mg ( n = 10 ) ] . The follow-up was monitored by a bladder diary and urodynamic evaluation . RESULTS Sixteen patients significantly decreased their incontinence episodes from 8 - 12 episodes before to 0 - 2 episodes during the doubled treatment . The reflex volume increased from 202 + /- 68 to 332 + /- 50 ml ( P < 0.001 ) . Cystometric capacity enlarged from 290 + /- 56 to 453 + /- 63 ml ( P < 0.001 ) . One patient had to stop the medication because of intolerable side effects and five patients did not experience satisfactory benefit . CONCLUSION The increased dosage of Tolterodine or Trospium is an effective treatment in patients with neurogenic bladder Objective : To determine the pharmacokinetics of oxybutynin and its main active metabolite , N-desethyloxybutynin , after multiple dosage ( 5 mg/30 ml three times daily ) of intravesical oxybutynin formulation . Furthermore , to determine the efficacy and safety of intravesical oxybutynin in the symptomatic relief of urge incontinence or urgency in adult patients with detrusor hyperreflexia or instability . Material and Methods : Nine patients were r and omly allocated to treatment with a special bladder instillation formulation of oxybutynin or placebo for two 14-day treatment periods in a double-blind , cross-over manner . The third , open study period was design ed for pharmacokinetic purpose s with all patients on the active drug . The pharmacokinetics was depicted by AUC 0 - 24 , C max , C min and t max . The efficacy was evaluated from the data collected from urinary voiding diaries and cystometries . The safety was measured by recording adverse events on question naires . Patients who were willing to continue with the intravesical oxybutynin treatment entered the 1-year extension part of the study . Results : Oxybutynin was absorbed from the bladder with a geometric mean C max of 9.4 ng/ml and AUC 0 - 24 of 92 ng*h/ml . For N-desethyloxybutynin , the geometric mean C max was 14.4 ng/ml and AUC 0 - 24 186 ng*h/ml . Elimination of the drug was protracted , as there were detectable serum concentrations of both oxybutynin and N-desethyloxybutynin even 24 hours postdose . The mean number of toilet visits/day decreased from the baseline value of 6.9 to 5.7 during oxybutynin treatment , whereas during the placebo period the value increased to 7.4 ( p = 0.022 ) . It remained at the same decreased level during the one-year follow-up period . Conclusions : Oxybutynin is readily absorbed from the bladder after intravesical administration . The serum concentrations of oxybutynin after single 5 mg intravesical doses are at least as high as those reported after oral drug intake , but the parent drug/ metabolite ratio is much higher after intravesical administration . The elimination of oxybutynin as well as its metabolite is prolonged after intravesical administration compared with that reported after oral drug intake . The mean number of daily toilet visits decreased significantly in the oxybutynin group Tolterodine is a potent antimuscarinic agent specifically developed for the treatment of urinary urge incontinence and other symptoms related to the overactive bladder . In order to assess the optimum dosage for use in future clinical studies , a double-blind , r and omized , placebo-controlled , parallel-group , multicenter study was performed in 90 patients with detrusor hyperreflexia and symptoms of urinary urgency , frequency , and /or urge incontinence . Urodynamic variables , micturition diary variables , and subjective urinary symptoms were measured before and after 2 weeks ' treatment with either placebo or tolterodine 0.5 , 1 , 2 , or 4 mg twice daily ( bd ) . Serum drug concentrations , electrocardiogram recordings , blood pressure , and incidence of adverse events were also assessed . Linear regression analysis showed a significant dose-response relationship for several clinical ly relevant urodynamic variables , while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of tolterodine . There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated , although 2 patients treated with a dosage of 4 mg bd experienced urinary retention that necessitated dosage reduction . The results of this study suggest that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor hyperreflexia . The optimum dosage of tolterodine for use in future studies is 1 - 2 mg bd PURPOSE We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis . MATERIAL S AND METHODS We performed a study to determine the most effective dose of atropine . Eight participants used increasing doses of intravesical atropine during a 12-day period . Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity ( voided/catheter volumes ) . We then did a r and omized , double-blind crossover trial . Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine , followed by 14 days of alternative treatment . Participants recorded a bladder diary and rated side effects and quality of life . The primary outcome variable was bladder capacity . RESULTS A total of 57 participants with multiple sclerosis completed the study . Average change in bladder capacity was higher in the atropine arm . The mean + /- SD oxybutynin change was 55.5 + /- 67.2 ml , the mean atropine change was 79.6 + /- 89.6 ml and the mean difference between arms was 24.1 ml ( 95 % CI -0.4 , 49.7 ; p = 0.053 ) . Changes in incontinence events and voiding frequency were not statistically different between the arms . Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm . CONCLUSIONS Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects . We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy , which often has troublesome side effects OBJECTIVE To compare trospium chloride ( TCl ) , a quaternary ammonium derivative with atropine-like effects and predominantly antispasmodic activity , with oxybutynin ( Oxy ) in terms of efficacy and adverse effects . PATIENTS AND METHODS In a r and omized , double-blind , multicentre trial , 95 patients with spinal cord injuries and detrusor hyper-reflexia were studied . Treatment consisted of three doses per day over a 2 week period , with either Oxy ( 5 mg three times daily ) or with TCl ( 20 mg twice daily ) with an additional placebo at midday . The results were evaluated with regard to changes in objective ( urodynamic ) data and subjective symptoms as well as the incidence/severity of adverse effects . RESULTS With both drugs there was a significant increase in maximum bladder capacity , a significant decrease in maximum voiding detrusor pressure and a significant increase in compliance and residual urine ; there were no statistically significant differences between the treatment groups . The percentage of patients who reported severe dryness of the mouth was considerably lower ( 4 % ) in those receiving TCl 2 x 20 mg/day than in those receiving Oxy ( 23 % ) 3 x 5 mg/day . Withdrawal from treatment was also less frequent in those receiving TCl ( 6 % ) than in those receiving Oxy ( 16 % ) . CONCLUSION Trospium chloride and oxybutynin , judged in terms of objective urodynamic parameters , are of substantially equal value as parasympathetic antagonists . However , assessment of tolerance in terms of adverse drug effects showed that TCl had certain advantages |
435 | 24,667,998 | Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC .
Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE .
Patients with FLE showed a larger impairment in PVF than patients with TLE , whereas on SVF there was no difference between FLE and TLE .
Semantic verbal fluency might not differentiate between FLE and TLE .
While verbal fluency impairment was anticipated , especially in left-sided TLE and FLE patients , the impairment in patients with right-sided TLE was larger than expected . | Testing of verbal fluency is currently part of st and ard presurgical neuropsychological assessment for patients with focal epilepsy .
However , to date no systematic review has been conducted on semantic ( SVF ) and phonemic verbal fluency ( PVF ) in this patient group .
The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction . | In most people the left hemisphere of the brain is dominant for language . Because of the increased incidence of atypical right-hemispheric language in left-h and ed neurological patients , a systematic association between h and edness and dominance has long been suspected . To clarify the relationship between h and edness and language dominance in healthy subjects , we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task . The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-h and edness , from 4 % in strong right-h and ers ( h and edness = 100 ) to 15 % in ambidextrous individuals and 27 % in strong left-h and ers ( h and edness = -100 ) . The relationship could be approximated by the formula : f1.gif " BORDER="0">. These results clearly demonstrate that the relationship between h and edness and language dominance is not an artefact of cerebral pathology but a natural phenomenon Objective : To evaluate the reliability of temporal and frontal functional MRI ( fMRI ) activation for the assessment of language dominance , as compared with the Wada test . Patients and Methods : Ten patients with temporal lobe epilepsy were studied using blood oxygen level dependent fMRI and echoplanar imaging ( 1.5-T ) . Three tasks were used : semantic verbal fluency , covert sentence repetition , and story listening . Data were analyzed using pixel by pixel autocorrelation and cross-correlation . fMRI laterality indices were defined for several regions of interest as the ratio ( L − R)/(L + R ) , L being the number of activated voxels in the left hemisphere and R in the right hemisphere . Wada laterality indices were defined as the difference in the percentages of errors in language tests between left and right carotid injections . Results : Semantic verbal fluency : The asymmetry of frontal activation was correlated with Wada laterality indices . The strongest correlation was observed in the pre central /middle frontal gyrus/inferior frontal sulcus area . Story listening : The asymmetry of frontal , but not temporal , activation was correlated with Wada laterality indices . Covert sentence repetition : No correlation was observed . Conclusions : There was a good congruence between hemispheric dominance for language as assessed with the Wada test and fMRI laterality indices in the frontal but not in the temporal lobes . The story listening and the covert sentence repetition tasks increased the sensitivity of detection of posterior language sites that may be useful for brain lesion surgery PURPOSE Selective amygdalohippocampectomy ( SAH ) is a surgical treatment option for patients with medically intractable mesial temporal lobe epilepsy . In contrast to st and ard anterior temporal lobectomy , resection of unaffected tissue is limited , although it achieves equal seizure outcomes in selected patients . In SAH , the mesial structures can be approached by different routes , the transsylvian approach and the transcortical approach . Advantages or disadvantages with respect to postoperative cognitive outcome are still a matter of debate . METHODS Eighty r and omized patients were included in the analyses . In 41 patients , the transsylvian approach , and in 39 patients , the transcortical approach was performed . All patients received comprehensive neuropsychological testing of verbal and nonverbal memory , attention , and executive functions before and 6 months or 1 year after SAH . RESULTS Seventy-five percent of patients became completely seizure free with no difference depending on the chosen approach . Repeated measures multivariate analysis of variance ( MANOVA ) showed that cognitive outcomes after both approaches were essentially the same . The only exception was phonemic fluency , which was significantly improved after transcortical but not after transsylvian SAH . CONCLUSIONS The results indicate that either surgical approach can be chosen independent of cognitive outcome criteria . Improvement in phonemic fluency after transcortical SAH may reflect selective normalization of cognitive function after epilepsy surgery , whereas frontal lobe manipulation might have hindered recovery of this function after transsylvian SAH OBJECT The aim of this study was to analyze the national health care burden of patients diagnosed with epilepsy in the US and to analyze any changes in the length of stay , mean charges , in-hospital deaths ( mortality ) , and disposition at discharge . METHODS A retrospective review of the Nationwide Inpatient Sample ( NIS ) data base for epilepsy admissions was completed for the years from 1993 to 2008 . The NIS is maintained by the Agency for Healthcare Research and Quality and represents a 20 % r and om stratified sample of all discharges from nonfederal hospitals within the U.S. Patients with epilepsy were identified using ICD-9 codes beginning with 345.XX . Approximately 1.1 million hospital admissions were identified over a span of 15 years . RESULTS Over this 15-year period ( between 1993 and 2008 ) , the average hospital charge per admission for patients with epilepsy has increased significantly ( p < 0.001 ) from $ 10,050 to $ 23,909 , an increase of 137.9 % . This is in spite of a 33 % decrease in average length of stay from 5.9 days to 3.9 days . There has been a decrease in the percentage of in-hospital deaths by 57.9 % and an increase in discharge to outside medical institutions . CONCLUSIONS The total national charges associated with epilepsy in 2008 were in excess of $ 2.7 billion ( U.S. dollars , normalized ) . During the studied period , the cost per day for patients rose from $ 1703.39 to $ 6130.51 . In spite of this drastic increase in health care cost to the patient , medical and surgical treatment for epilepsy has not changed significantly , and epilepsy remains a major source of morbidity Over an 18-month period , all incident cases of neurological disorders were ascertained prospect ively in an unselected urban population based in 13 general practice s in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery . In three of these practice s , the lifetime prevalence of neurological disorders was also assessed . A population of 100 230 patients registered with participating general practice s was followed prospect ively for the onset of neurological disorders . Multiple methods of case finding were used to maintain accuracy . The age- and sex-adjusted incidence rates of neurological disorders were calculated . The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients . The age- and sex-adjusted incidence rates were calculated for major neurological conditions . [ These are expressed as rates per 100 000 persons per annum , with 95 % confidence intervals ( CI ) in parentheses ] . The commonest of these were first cerebrovascular events , 205 ( CI : 183 , 230 ) ; shingles , 140 ( CI : 104 , 184 ) ; diabetic polyneuropathy , 54 ( CI : 33 , 83 ) ; compressive neuropathies , 49 ( CI : 39 , 61 ) ; epilepsy , 46 ( CI : 36 , 60 ) ; Parkinson 's disease , 19 ( CI : 12 , 27 ) ; peripheral neuropathies , 15 ( CI : 9 , 23 ) ; CNS infections , 12 ( CI : 5 , 13 ) ; post-herpetic neuralgia , 11 ( CI : 6 , 17 ) ; and major neurological injuries , 10 ( CI : 4 , 11 ) . Lifetime prevalence rates are also reported ( expressed as rate per 1000 persons with 95 % CI ) . The most prevalent conditions were : completed stroke , 9 ( CI : 8 , 11 ) ; transient ischaemic attacks , 5 ( CI : 4 , 6 ) ; active epilepsy , 4 ( CI : 4 , 5 ) ; congenital neurological deficit , 3 ( CI : 3 , 4 ) ; Parkinson 's disease , 2 ( CI : 1 , 3 ) ; multiple sclerosis , 2 ( CI : 2 , 3 ) ; diabetic polyneuropathy , 2 ( CI : 1 , 3 ) ; compressive mononeuropathies , 2 ( CI : 2 , 3 ) ; and sub-arachnoid haemorrhage , 1 ( CI : 0.8 , 2 ) . Overall , the onset of 625 neurological disorders was observed per 100 000 population annually . Six percent of the population had at some time had a neurological disorder . This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times ; we found that these disorders give rise to significant morbidity in the community The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy ( TLE ) . Eighteen patients with left TLE , 18 with right TLE , and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language ( covert semantic verbal fluency , covert sentence repetition , and story listening ) . Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices ( LI ) . Atypical lateralization was defined as a right-sided LI ( LI<-0.20 ) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task . Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task , whereas activation was less lateralized to the left hemisphere in left TLE patients , although the difference did not reach significance . In the story listening and the repetition tasks , activation was significantly more right sided in the temporal lobes of patients with left TLE . Atypical language representation was found in 19 % of TLE patients ( five left and two right TLE ) . The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization . Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns , suggesting that this reorganization may represent a compensatory mechanism WE examined whether 53 adult non-aphasic patients with either left ( 22 ) or right temporal lobe lesions ( 31 ) demonstrate dissociable patterns of hemispheric asymmetries in category-specific word fluency tasks . The patients were asked to articulate as many appropriate words as possible within 60 or 90 s in response to six target categories . There was no effect of patient groups on the overall fluency . However , patients with a leftsided temporal lobe lesion were impaired retrieving words to ‘ initial letters ’ and to the category ‘ animals ’ . Right temporal lobe patients were impaired retrieving ‘ tools ’ and words referring to specific visual attributes . There were no fluency differences for ‘ food-supermarket goods ’ and ‘ flat interior ’ . We conclude that temporal lobe damage can result in category-specific impairments in word retrieval depending on the affected hemisphere BACKGROUND R and omized trials of surgery for epilepsy have not been conducted , because of the difficulties involved in design ing and implementing feasible studies . The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy . We conducted a r and omized , controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy . METHODS Eighty patients with temporal-lobe epilepsy were r and omly assigned to surgery ( 40 patients ) or treatment with antiepileptic drugs for one year ( 40 patients ) . Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients ' treatment assignments . The primary outcome was freedom from seizures that impair awareness of self and surroundings . Secondary outcomes were the frequency and severity of seizures , the quality of life , disability , and death . RESULTS At one year , the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group ( P<0.001 ) . The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life ( P<0.001 for both comparisons ) than the patients in the medical group . Four patients ( 10 percent ) had adverse effects of surgery . One patient in the medical group died . CONCLUSIONS In temporal-lobe epilepsy , surgery is superior to prolonged medical therapy . R and omized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects OBJECTIVES The correlation between clinical measures of memory and subjectively reported memory is often poor . Regarding this we investigated in patients with temporal lobe epilepsy ( TLE ) whether there is evidence that persons mistake other cognitive performances for memory due to subjective memory theories . METHODS a neuropsychological test battery comprising measures of attention , verbal/figural memory and other visual or language related functions was applied in patients with left ( L-TLE , n=24 ) or right temporal lobe epilepsy ( R-TLE , n=21 ) and healthy volunteers ( n=20 ) . In addition , subjective self- and other-reported memories were assessed by the subjective memory question naire ( SMQ ) . RESULTS subjective measures as well as objective measures indicate significant cognitive impairment in TLE and in L-TLE in particular . Self-reports and other-reports are interrelated but only self-reported memory correlates significantly with objective memory performance . Regression analysis indicates that self-reported memory is best predicted by word fluency followed by verbal memory and vocabulary , and other-reported memory is best predicted by word fluency , vocabulary , confrontation naming , and verbal recognition memory . DISCUSSION The results suggest that attribution of memory refers to a subjective view of memory which is wider than its neuropsychological definition . It furthermore differs dependent on the observer 's point of view . Memory is preferentially concluded from verbal behaviors . These reflect language skills and access to vocabulary rather than declarative memory . Consideration of subjective memory theories and associated attribution processes can significantly contribute to our underst and ing of the often-poor relationship between objective test results and subjective impairment in TLE This study represents the first prospect i ve controlled investigation of preoperative versus postoperative ( 6 months ) language function in patients who underwent partial resection of the dominant ( n = 15 ) or nondominant ( n = 14 ) anterior temporal lobe for treatment of medically refractory epilepsy . Language dominance was confirmed by in tracarotid sodium amytal test . Thirteen of the 15 patients undergoing anterior temporal lobectomy of the dominant hemisphere were operated on under local anesthesia in order to map language and memory functions intraoperatively . Using a st and ardized language /aphasia battery , we found a significant trend of worse preoperative language function in patients with dominant hemisphere temporal lobe foci in comparison to patients with nondominant foci . Following anterior temporal lobectomy , neither group showed any significant losses in language function , whereas the dominant hemisphere temporal lobe group showed significant improvement in receptive language comprehension and associative verbal fluency While most neuropsychological studies in focal epilepsies are concerned with temporal lobe epilepsy ( TLE ) , only few investigations aim cognitive functioning in unresected patients with frontal lobe epilepsy ( FLE ) . Following functional models arising from lesional studies , we evaluated patients with TLE ( 21 left , 17 right ) and FLE ( 6 left , 17 right ) with respect to attention and speed , motor coordination , verbal/nonverbal fluency , concept formation , response inhibition , anticipatory behavior and memory span . The following results were obtained . When compared to TLE , FLE was associated with significantly poorer results in almost all tests , fluency tests being the exception . No group differences were found with respect to the lateralization of the epileptic focus or the presence or absence of cerebral lesions . Factor analysis of the tests indicated that different subfunctions ( speed , STM , motor coordination , response maintenance and inhibition ) were assessed . A particular cognitive pattern of impaired motor coordination or response inhibition appeared to be characteristic for patients with FLE |
436 | 24,390,417 | The findings from meta- analysis showed that excess BMI was positively correlated with BCR of PCa multifacetedly , indicating good weight control and detailed attention to treating obese patients might improve the prognosis of PCa | Abstract Obesity is inconsistently related to biochemical recurrence ( BCR ) of prostate cancer ( PCa ) in different epidemiological studies .
We conducted a systematic review and dose – response meta- analysis of published studies from MEDLINE and EMBASE in order to determine the relationship between body mass index ( BMI ) and BCR of PCa . | PURPOSE Several retrospective analyses have suggested that obese men with prostate cancer treated with external beam radiotherapy ( EBRT ) have outcomes inferior to those of normal-weight men . However , a recently presented analysis for the first time challenged this association between body mass index ( BMI ) and treatment failure . It is therefore important to provide further data on this issue . METHODS AND MATERIAL S This was a retrospective analysis of 564 men treated with risk-adapted conformal EBRT at a single institution . Low-risk patients received EBRT alone , and the other patients received EBRT plus endocrine treatment . In addition , high-risk patients were treated to higher EBRT doses ( 74 Gy ) . A rectal balloon catheter for internal immobilization , which can be identified on portal images , was used in 261 patients ( 46 % ) . Thus , localization did not rely on bony l and marks alone in these cases . RESULTS The median BMI was 26 , and 15 % of patients had BMI ≥30 . Neither univariate nor multivariate analyses detected any significant impact of BMI on biochemical relapse , prostate cancer-specific survival , or overall survival . The 5-year biochemical relapse rate was 21 % and prostate cancer-specific survival 96 % . CONCLUSIONS The present analysis of a large cohort of consecutively treated patients suggests that efforts to reduce prostate movement and geographic miss might result in comparable outcomes in obese and normal-weight patients PURPOSE Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis , especially in tumor progression . The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index ( BMI ) as a measure of obesity . EXPERIMENTAL DESIGN We carried out a prospect i ve study of 526 patients registered at the M.D. And erson Cancer Center from 1992 to 2001 . Kaplan-Meier and Cox proportional hazard analyses were done . RESULTS During an average follow-up of 54 months , 97 ( 18 % ) post-prostatectomy patients experienced biochemical failure . Patients who were obese ( BMI > or = 30 kg/m2 ) at diagnosis had a higher rate of biochemical failure than nonobese men ( P = 0.07 ) . Those obese at 40 years had an even greater rate of biochemical failure ( P = 0.001 ) . Higher BMI at diagnosis [ hazard ratio ( HR ) , 1.07 ; P = 0.01 ] and Gleason score = 7(4 + 3 ) and > or = 8 ( HR , 3.9 ; P = 0.03 and HR , 10.0 ; P < or = 0.001 , respectively ) remained significant independent predictors of biochemical failure in multivariate analysis . Men who gained weight at the greatest rate ( > 1.5 kg/y ) between 25 years and diagnosis progressed significantly sooner ( mean time , 17 months ) than those who exhibited a slower weight gain ( mean time , 39 months ; P(trend ) = 0.005 ) . The inclusion of obesity to the clinical nomogram improved performance . CONCLUSIONS Our findings vali date the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited Increasing body mass index ( BMI ) is associated with shorter time to prostate‐specific antigen ( PSA ) failure after radical prostatectomy . Whether BMI is associated with time to PSA failure was investigated in men treated with and rogen suppression therapy ( AST ) and radiation therapy ( RT ) for clinical ly localized prostate cancer OBJECTIVE To evaluate the impact of obesity on the outcomes of laparoscopic radical prostatectomy . METHODS AND MATERIAL S In a prospect i ve urologic cancer data base , 765 patients underwent extraperitoneal laparoscopic radical prostatectomy for localized prostate cancer . The patients were categorized into 3 groups of body mass index ( kg/m(2 ) ) : < 25.0 ( n = 276 , 30 % , " normal weight " ) , 25.0 to 30.0 ( n = 365 , 48 % , " overweight " ) and > 30.0 ( n = 124 , 16 % , " obese " ) . We assessed the perioperative , oncological , and functional outcomes in this cohort of patients . Preoperative and postoperative evaluation of continence and erectile function were performed using vali date d question naires . RESULTS Mean operative time was significantly longer in obese patients ( P < .001 ) and blood loss was also more important ( P < .01 ) . The obese patients had the highest likelihood of having aggressive tumors : nonorgan confined prostate cancer ( 49 % , P = .002 ) and Gleason score ≥ 7 ( 80 % , P = .005 ) . The obese group had the higher positive surgical margins rate ( overall : 27 % , P = .012 ; pT2 : 20 % , P = .02 ) . With a mean follow-up of 38 months , obesity was not an independent predictive factor of biochemical recurrence . At the 12-month follow-up , 85 % , 74 % , and 72 % of normal , overweight , and obese men , respectively , were continent ( no pad ) ( P = .04 ) . At the 12-month follow-up , 57 % , 58 % , and 40 % of normal , overweight , and obese men , respectively , reported an erection sufficient for intercourse ( P = .01 ) . CONCLUSION Laparoscopic radical prostatectomy is a safe and effective procedure in obese men with midterm cancer control . However , obese patients are at higher risk of aggressive disease . Recovery of continence and potency in these patients are significantly lower compared to nonobese men |
437 | 16,093,854 | Advanced bladder cancer is one tumor type in which EBM principles can be applied to determine the best treatment option | For the physician , external evidence is commonly in the form of published literature , for which there are various types : systematic review s and meta-analyses of r and omized controlled trials ( RCTs ) , non-r and omized controlled trials , case reports , clinical examples and consensus meetings [ 4 ] .
Generally , RCTs provide the most reliable data by limiting potential biases and confounding factors .
Combining the data from multiple RCTs , as is done in meta-analyses , can potentially yield greater statistical power to find differences in outcomes between therapeutic choices . | PURPOSE To evaluate the efficacy and toxicity of weekly paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma ( TCC ) of the urothelial tract . PATIENTS AND METHODS Patients with advanced unresectable TCC were enrolled onto this multicenter , community-based , phase II trial . Initially , patients were treated with paclitaxel 110 mg/m(2 ) and gemcitabine 1,000 mg/m(2 ) by intravenous infusion on days 1 , 8 , and 15 every 28 days . Patients who had an objective response or stable disease continued treatment for a maximum of six courses . Paclitaxel was decreased to 90 mg/m(2 ) and gemcitabine was decreased to 800 mg/m(2 ) for the last 12 patients because of a concerning incidence of pulmonary toxicity in the first 24 patients . RESULTS Thirty-six patients were enrolled between September 1998 and March 2003 . Twenty-four patients received the higher doses of paclitaxel and gemcitabine , and 12 patients received the lower doses . Twenty-five ( 69.4 % ) of 36 patients had major responses to treatment , including 15 patients ( 41.7 % ) with complete responses . With a median follow-up time of 38.7 months , the median survival time was 15.8 months . Grade 3 and 4 toxicities included granulocytopenia ( 36.1 % ) , thrombocytopenia ( 8.3 % ) , and neuropathy ( 16.7 % ) . Five patients ( 13.9 % ) had grade s 3 to 5 pulmonary toxicity , and one patient had grade 2 pulmonary toxicity . CONCLUSION Weekly paclitaxel and gemcitabine is an active regimen in the treatment of patients with advanced TCC . However , because of the high incidence of pulmonary toxicity associated with this schedule of paclitaxel and gemcitabine , we recommend against the use of this regimen in this patient population Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality . In particular , patients with metastatic disease have a poor prognosis , with less than 5 % alive at 5 years . A multicentre r and omized trial comparing methotrexate and vinblastine ( MV ) with cisplatin , methotrexate and vinblastine ( CMV ) in advanced or metastatic transitional cell carcinoma was conducted in the UK . From April 1991 to June 1995 , 214 patients were entered by 16 centres , 108 r and omized to CMV and 106 to MV . A total of 204 patients have died . The hazard ratio ( relative risk of dying ) was 0.68 ( 95 % CI 0.51 - 0.90 , P-value = 0.0065 ) in favour of CMV . This translates to an absolute improvement in 1-year survival of 13 % , 16 % in MV and 29 % in CMV . The median survival for CMV and MV was 7 months and 4.5 months respectively . Two hundred and eight patients objective ly progressed or died . The hazard ratio was 0.55 ( 95 % CI 0.41 - 0.73 , P-value = 0.0001 ) in favour of CMV . Two hundred and nine patients symptomatically progressed or died . The hazard ratio was 0.48 ( 95 % CI 0.36 - 0.64 , P-value = 0.0001 ) in favour of CMV . The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease . These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups . We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma , taking into account the increased toxicity PURPOSE To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium . PATIENTS AND METHODS Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance . All patients received recombinant human granulocyte colony-stimulating factor ( rhG-CSF ) at 5 micrograms/kg/d for at least 10 days during each cycle . RESULTS Eleven of 26 patients ( 42 % ; 95 % confidence interval [ CI ] , 23 % to 63 % ) demonstrated an objective response , with seven achieving a complete clinical response ( CR ) ( 27 % ; 95 % CI , 12 % to 48 % ) and four ( 15 % ) a partial response ( PR ) . The median duration of response in the 11 responders is 7 + months ( range , 4 to 17 ) , with five responders ( four CRs , one PR ) remaining progression-free at 5 , 6 , 10 , 12 , and 16 months from the start of therapy . The estimated median survival duration for all patients is 8.4 months . Hematologic toxicity consisted of anemia ( 12 % grade 3 ) and granulocytopenia ( 4 % grade 3 , 19 % grade 4 ) , with two patients developing granulocytopenic fevers . Nonhematologic toxicity included grade 3 mucositis in 11 % , grade 3 neuropathy in 11 % , and grade 4 diarrhea in 4 % . CONCLUSION Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma , and is well tolerated by this patient population when given with hematopoetic growth factor support PURPOSE To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract . PATIENTS AND METHODS Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered , community-based , phase II trial between May 1997 and December 1999 . All patients were treated with paclitaxel 200 mg/m(2 ) by 1-hour intravenous ( IV ) infusion on day 1 and gemcitabine 1,000 mg/m(2 ) IV on days 1 , 8 , and 15 ; courses were repeated every 21 days . Patients who had objective response or stable disease continued treatment for six courses . RESULTS Twenty-nine of 54 patients ( 54 % ; 95 % confidence interval , 40 % to 67 % ) had major responses to treatment , including 7 % complete responses . With a median follow-up of 24 months , 16 patients ( 30 % ) remain alive and nine ( 17 % ) are progression-free . The median survival for the entire group was 14.4 months ; 1- and 2-year actuarial survival rates were 57 % and 25 % , respectively . Seven ( 47 % ) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine . Grade 3/4 toxicity was primarily hematologic , including leukopenia ( 46 % ) , thrombocytopenia ( 13 % ) , and anemia ( 28 % ) . Ten patients ( 19 % ) required hospitalization for neutropenia and fever , and one patient had treatment-related septic death . CONCLUSION The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract . Response rate and duration compare favorably with those produced by other active , first-line regimens . This regimen should be further evaluated in phase II and III studies , as well as in patients with compromised renal function The carboplatin‐based chemotherapeutic regimen M‐CAVI ( methotrexate , carboplatin , and vinblastine ) is active against bladder carcinoma and can be administered to patients who are ineligible to receive cisplatin or doxorubicin . The authors design ed a r and omized study to evaluate whether M‐CAVI offers a therapeutic advantage over the cisplatin‐based regimen M‐VAC ( methotrexate , vinblastine , doxorubicin , and cisplatin ) in the treatment of patients with surgically incurable advanced bladder carcinoma |
438 | 27,321,374 | The interval to surgery after neoadjuvant therapy and preoperative radiotherapy ( short or long course ) was not associated with an increased incidence of postoperative AL .
Conclusion Neoadjuvant therapy does not appear to increase the incidence of postoperative AL after anterior resection for mid and low rectal cancer .
In addition , neither the interval to surgery after neoadjuvant therapy nor the radiotherapy regimen increases the rate of postoperative AL | Aim The aim was to evaluate the association of neoadjuvant therapy with increases in the incidence of anastomotic leakage ( AL ) after middle and low rectal anterior resection . | OBJECTIVE To determine perioperative morbidity , survival , and local failure rates in a large group of consecutive patients with rectal cancer undergoing low anterior resection by multiple surgeons on a specialty service . The primary objective was to assess the surgical complications associated with preoperative radiation sequencing . SUMMARY BACKGROUND DATA The goals in the treatment of rectal cancer are cure , local control , and preservation of sphincter , sexual , and bladder function . Surgical resection using sharp perimesorectal dissection is important for achieving these goals . The complications and mortality rate of this surgical strategy , particularly in the setting of preoperative chemoradiation , have not been well defined . METHODS There were 1233 patients with primary rectal cancer treated at the authors ' cancer center from 1987 to 1995 . Of these , 681 underwent low anterior resection and /or coloanal anastomosis for primary rectal cancer . The surgical technique used the principles of sharp perimesorectal excision . Morbidity and mortality rates were compared between patients receiving preoperative chemoradiation ( Preop RT , n = 150 ) and those not receiving preoperative chemoradiation ( No Preop RT , n = 531 ) . Recurrence and survival data were determined in patients undergoing curative resection ( n = 583 , 86 % ) among three groups of patients : those receiving Preop RT ( n = 131 ) , those receiving postoperative chemoradiation ( Postop RT , n = 110 ) , and those receiving no radiation therapy ( No RT , n = 342 ) . RESULTS The perioperative mortality rate was 0.6 % ( 4/681 ) . Postoperative complications occurred in 22 % ( 153/681 ) . The operative time , estimated blood loss , and rate of pelvic abscess formation without associated leak were higher in the Preop RT group than the No Preop RT group . However , the overall complication rate , rate of wound infection , anastomotic leak , and length of hospital stay were no different between Preop RT and No Preop RT patients . With a median follow-up of 45.6 months , the overall actuarial 5-year recurrence rate for patients undergoing curative resection ( n = 583 ) was 19 % , with 4 % having local recurrence only , 12 % having distant recurrence , and 3 % having both local and distant recurrence , for an overall local recurrence rate of 7 % . The actuarial 5-year overall survival rate was 81 % ; the disease-free survival rate was 75 % and the local recurrence rate was 10 % . The overall survival rate was similar between Preop RT ( 85 % ) , Postop RT ( 72 % ) , and No RT ( 83 % ) patients ( p = 0.10 ) , whereas the disease-free survival rate was significantly worse for Postop RT ( 65 % ) patients compared with Preop RT ( 79 % ) and No RT ( 77 % ) patients ( p = 0.04 ) . CONCLUSION The use of preoperative chemoradiation results in increased operative time , blood loss , and pelvic abscess formation but does not increase the rate of anastomotic leaks or the length of hospital stay after low anterior resection for rectal cancer . The 5-year actuarial overall survival rate for patients undergoing curative resection exceeded 80 % , with a local recurrence rate of 10 % Aim The st and ard treatment for patients with clinical ly resectable rectal cancer is surgery . Postoperative radiochemotherapy ( RCT ) is recommended for advanced disease ( pT3/4 or pN+ ) . In recent years , encouraging results of pre‐operative radiotherapy have been reported . This prospect i ve r and omized phase‐III‐trial ( CAO/ARO/AIO‐94 ) compares the efficacy of neoadjuvant RCT to st and ard postoperative RCT . We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity Introduction Total mesorectal excision ( TME ) with preoperative chemoradiation therapy is an accepted st and ard treatment for low rectal cancer . Although the laparoscopic approach is accepted for the treatment of colon cancer , its value for low rectal cancer is unknown . The purpose of this study was to evaluate whether preoperative chemoradiation therapy exerted an adverse influence on laparoscopic TME for low rectal cancer . Methods We studied 125 consecutive patients who underwent laparoscopic TME for low rectal cancer . Twenty patients with preoperative chemoradiation therapy ( CRT-Lap group ) were compared with 105 patients without chemoradiation therapy ( non-CRT-Lap group ) . Results Operating time in the CRT-Lap group ( 276 min , range 160–390 min ) was no different from that in the non-CRT-Lap group ( 263 min , range 143–456 min ) . The CRT-Lap group had more blood loss during the operation ( 70 vs. 37 ml ) , but mean blood loss was < 100 ml . The distal tumor margin was longer in the CRT-Lap group ( 25.8 vs. 18.6 mm ) . The number of lymph node harvested did not differ between the groups ( 14.5 vs. 15.4 ) . Conversion to open surgery was necessary only in one case in the non-CRT-Lap group . There was no anastomotic leakage in the CRT-Lap group , whereas three patients ( 3.1 % ) had anastomotic leakage in the non-CRT-Lap group . Conclusion Laparoscopic TME with preoperative chemoradiation therapy is a safe procedure with reasonable operating time and does not appear to pose any threat to the surgical and oncologic outcomes Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer . However , improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed . We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy . Methods We undertook a r and omised trial in 80 centres in four countries . 1350 patients with operable adenocarcinoma of the rectum were r and omly assigned , by a minimisation procedure , to short-course preoperative radiotherapy ( 25 Gy in five fractions ; n=674 ) or to initial surgery with selective postoperative chemoradiotherapy ( 45 Gy in 25 fractions with concurrent 5-fluorouracil ) restricted to patients with involvement of the circumferential resection margin ( n=676 ) . The primary outcome measure was local recurrence . Analysis was by intention to treat . This study is registered , number IS RCT N 28785842 . Findings At the time of analysis , which included all participants , 330 patients had died ( 157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy ) , and median follow-up of surviving patients was 4 years . 99 patients had developed local recurrence ( 27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy ) . We noted a reduction of 61 % in the relative risk of local recurrence for patients receiving preoperative radiotherapy ( hazard ratio [ HR ] 0·39 , 95 % CI 0·27–0·58 , p<0·0001 ) , and an absolute difference at 3 years of 6·2 % ( 95 % CI 5·3–7·1 ) ( 4·4 % preoperative radiotherapy vs 10·6 % selective postoperative chemoradiotherapy ) . We recorded a relative improvement in disease-free survival of 24 % for patients receiving preoperative radiotherapy ( HR 0·76 , 95 % CI 0·62–0·94 , p=0·013 ) , and an absolute difference at 3 years of 6·0 % ( 95 % CI 5·3–6·8 ) ( 77·5 % vs 71·5 % ) . Overall survival did not differ between the groups ( HR 0·91 , 95 % CI 0·73–1·13 , p=0·40 ) . Interpretation Taken with results from other r and omised trials , our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada BACKGROUND In many patients with rectal cancer , defunctioning stomas are created to limit the consequences of anastomotic leakage . Although intended to be temporary , a substantial proportion of these stomas might never be reversed for various reasons . We aim ed to describe stoma policy by use of data from the total mesorectal excision ( TME ) trial in patients with rectal cancer and to identify factors that limit stoma reversal . METHODS 924 Dutch patients with rectal cancer who underwent a low anterior resection were selected from the TME trial , a prospect i ve , r and omised multicentre trial study ing the effects of short-term preoperative radiotherapy in 1861 patients who underwent TME . Creation of stomas and time to stoma reversal were analysed retrospectively by use of multivariate analysis . FINDINGS In 523 of 924 ( 57 % ) patients , a primary stoma ( defined as a stoma created at the time of TME ) was constructed after a low anterior resection . Geographical differences in the number of primary stomas constructed were reported throughout the Netherl and s. 19 % of stomas that were created were never reversed . Postoperative complications and secondary constructed stomas ( defined as a stoma created during a second or subsequent procedure after TME ) were associated with a high likelihood of a permanent stoma . However , perioperative complications were not a limiting factor for stoma closure . INTERPRETATION Postoperative complications are an important limiting factor for stoma reversal because , after occurrence of these complications , patients and surgeons might be reluctant to reverse the stoma , so a substantial proportion of these stomas are never closed . Future guidelines for stoma creation and closure should consider these factors BACKGROUND We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer . However , little is known about its possible changes in response to radiotherapy ( RTX ) , which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis . We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy sample s of tumor and normal mucosa tissue before and after RTX . METHODS Biopsy sample s were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy . The following parameters were analyzed by immunohistochemistry , flow cytometry , or quantitative real-time polymerase chain reaction : Microvessel density , leukocyte infiltration , proliferating epithelial and tumor cells , proliferating endothelial cells , adhesion molecule expression on endothelial cells , and the angiogenic mRNA profile . RESULTS The tumor biopsy sample s taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells ( p < 0.001 ) . In contrast , the leukocyte infiltration , the levels of basic fibroblast growth factor in carcinoma tissue , and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly ( p < 0.05 ) . CONCLUSION Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation , RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration . This suggests the possibility that , in addition to its direct cytotoxic effect , radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers Although many trials have shown the efficacy of preoperative chemoradiotherapy ( CRT ) or postoperative CRT compared with surgery alone , the optimal sequence of radiotherapy and surgery is unclear . The authors reported the final results of this single institution prospect i ve r and omized phase 3 trial comparing preoperative CRT with postoperative CRT using capecitabine in survival , local control , sphincter preservation , and toxicity for the treatment of locally advanced rectal cancer Purpose This study was undertaken to determine whether neoadjuvant radiotherapy is associated with an increased risk of anastomotic leak for rectal cancer patients undergoing restorative resection . Methods From 1980 to 2010 , patients who underwent restorative resection for rectal cancer ( tumors within 15 cm of anal verge ) were identified from a prospect i ve institutional data base and grouped based on whether they received neoadjuvant radiotherapy ( + RT ) or not ( −RT ) . The main outcome was anastomotic leak documented by imaging ( contrast leak ) , intra-operative or clinical ( signs of peritonitis ) findings and confirmed by staff surgeon assessment . Using multivariate ( MV ) analysis risk factors for leak were identified , presented as OR ( 95 % CI ) . Results One thous and eight hundred sixty-two patients were included in the analysis , 28 % in the + RT group . Eighty-six percent of + RT patients received neoadjuvant chemoradiotherapy . The overall leak rate was 6.3 % , with no significant difference in + RT and −RT groups ( 8 % vs 5.7 % , p = 0.06 ) . The + RT group had a lower mean age at surgery ( 58 vs 63 year , p < 0.001 ) , more male ( 75 % vs 62 % , p < 0.001 ) and more ASA 3/4 ( 44 % vs 35 % , p < 0.001 ) patients , greater use of defunctioning ostomy ( 87 % vs 44 % , p < 0.001 ) and colo-anal anastomosis ( 77 % vs 34 % , p < 0.001 ) . Mean tumor distance from the anal verge was lower in + RT group ( 6.6 vs 9.7 cm , p < 0.001 ) . On MV analysis , male sex ( OR 1.64 ( 1.03–2.62 ) , p = 0.038 ) , ASA 4 ( OR 4.70 ( 2.07–10.7 ) , p < 0.001 ) , tumor distance from anal verge ≤ 5 cm ( OR 2.49 ( 1.37–4.52 ) , p = 0.003 ) , and tumor size at surgery ≥ 4 cm ( OR 1.75 ( 1.15–2.65 ) , p = 0.009 ) were independently associated with leak . + RT was not independently associated with leak ( OR 1.44 ( 0.85–2.46 ) , p = 0.18 ) , while defunctioning ostomy did not reduce leak occurrence ( OR 0.75 ( 0.44–1.28 ) , p = 0.29 ) . Conclusions The findings suggest that neoadjuvant radiotherapy is not independently associated with an anastomotic leak for rectal cancer patients undergoing restorative resection and support a selective policy towards the use of a defunctioning ostomy on a case by case basis based on intra-operative judgment and consideration of tumor location , size , and patient characteristics Between March 1987 and February 1990 , 1168 patients with resectable rectal cancer were recruited into a nationwide Swedish trial . Patients were r and omly allocated to receive either preoperative irradiation ( 25 Gy infive fractions over 1 week ) followed by surgery within 1 week , or surgery alone . In each group 454 patients underwent curative surgery . The groups were well matched for age , sex and surgical procedure . The postoperative mortality rates did not differ : 4 per cent after irradiation versus 3 per cent after surgery alone , but the postoperative mortality rate was significantly higher in patients treated with a two‐ rather than three‐ or four‐portal technique ( 15 versus 3 per cent , P < 0·001 ) . More perineal wound infections were found in patients receiving irradiation ( 20 versus 10 per cent , P < 0·001 ) . No difference in the incidence of anastomotic dehiscence or other postoperative complication was found between the groups . Preoperative radiotherapy with a short‐term high‐dose technique can be delivered without major acute adverse effects , provided the irradiation technique is optimized Background . From 1980 to 1987 , 849 patients with clinical ly resectable rectal adenocarcinoma were r and omized into a controlled clinical trial to evaluate the role of preoperative radiotherapy INTRODUCTION Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality . The long-term prognosis of anastomotic leakage is poorly documented . This study was design ed to assess whether anastomotic leakage affects five-year survival and local recurrence . METHODS A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 ( prospect i ve data , 5-year follow-up ) . The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test . RESULTS A total of 1,834 patients underwent a curative resection with an anastomosis ( anastomotic leak = 71 ; 3.9 percent ) : 30-day mortality : 18.3 percent in the leak group , and 3.5 percent in the nonleak group ( P < 0.001 ) ; local recurrence : 19 percent in the leak group , and 9.8 percent in the nonleak group ( P = 0.018 ) . A total of 1,201 patients underwent colonic anastomosis ( anastomotic leak = 31 ; 2.6 percent ) . There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups . A total of 633 patients underwent rectal anastomosis ( anastomotic leakage = 40 ; 6.3 percent ) : 30-day mortality : 10 percent in the leak group , and 2 percent in the nonleak group ( P = 0.014 ) ; cumulative five-year estimate of local recurrence : 25.1 ( 95 percent confidence interval , 9.6–40.5 ) percent in the leak group , and 10.4 ( 95 percent confidence interval , 7.7–13 ) percent in the nonleak group ( P = 0.007 ) . Cumulative five-year estimate of overall survival : 52.8 ( 95 percent confidence interval , 36.1–69.4 ) percent in the leak group , and 63.9 ( 95 percent confidence interval , 59.9–67.9 ) percent in the nonleak group ( P = 0.19 ) . CONCLUSIONS After rectal anastomosis , an anastomotic leak is associated with a significant increase in local recurrence BACKGROUND A pathologic complete response ( pCR ) can be observed in up to 25 % of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis . However , few data are available regarding the effect of pCR on postoperative morbidity . This study aim ed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision ( TME ) . METHODS A prospect ively maintained data base ( 2006 - 2011 ) was review ed for all consecutive patients ( n = 143 ) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy . Postoperative data were compared for pCR-group and non-pCR-group . A pCR was defined as the absence of gross and microscopic tumor in the specimen , irrespective of the nodal status ( ypT0 ) . RESULTS Thirty-three patients ( 23 % ) had a pCR . Median operating time was greatly shorter in the pCR-group ( 230 minutes , 180 - 360 ) , compared with the non-pCR-group ( 240 minutes , 130 - 420 , P = .02 ) . Lymph node involvement was noted for 12 % of the patients in the pCR-group and 33 % of the patients in the non-pCR-group ( P = .91 ) . Clavien Dindo grade 3 and 4 complications ( 6 % vs 22 % , P = .04 ) , infection related morbidity ( 47 % vs 76 % , P = .04 ) , and clinical anastomotic leakage rates ( 9 % vs 29 % , P = .02 ) were lesser in the pCR group compared with the non-pCR group . Mean duration of hospital stay was lesser in the pCR-group ( 9 vs 12 days , P = .01 ) . CONCLUSION This study showed that Clavien Dindo grade 3 and 4 complications , including anastomosis leakage , and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer Introduction R and omized trials have demonstrated a reduction in local recurrence rate in rectal cancer patients treated with preoperative chemoradiotherapy and total mesorectal excision ( TME ) compared to patients undergoing TME alone . Accordingly , preoperative chemoradiotherapy in all UICC stages II and III rectal cancers has been recommended in the German treatment guidelines as of 2004 . However , this policy has been question ed in recent years , partly due to concern regarding an increase in postoperative complications through preoperative therapy . Studies on this issue are sparse ; most have been conducted in specialized centers , included relatively few patients , and yielded partly contradicting results . It was the aim of our analysis to investigate the influence of preoperative chemoradiotherapy on anastomotic leak rate and postoperative bladder dysfunction in rectal cancer patients using a representative data set from the Quality Assurance in Rectal Cancer Surgery multicenter observational trial . Method This is a retrospective analysis of data from the Quality Assurance in Rectal Cancer Surgery prospect i ve multicenter observational trial . Data of all patients undergoing curatively intended sphincter-preserving resection for UICC stage I through III rectal carcinoma between 01 Jan 2005 and 31 Dec 2007 with or without preoperative chemoradiotherapy ( groups A and B , respectively ) were included . Multivariate statistical analysis using propensity score analysis was carried out regarding outcome parameters total anastomotic leak rate , rate of anastomotic leaks requiring reoperation , and postoperative bladder dysfunction . Results A total of 2,085 patients were included ( group A , n = 676 , group B , n = 1,409 ) . Significant differences were present between groups regarding age , sex , distance of the tumor from the anal verge , pT-stage , UICC stage , hepatic risk factors , and use of protective enterostomy by univariate analysis . Multivariate logistic regression including these parameters was used to calculate the propensity score ( likelihood to be assigned to group A or B as a consequence of the individual profile of these factors ) for each patient . When outcome parameters were compared between groups A and B after stratification for propensity score , no significant differences regarding postoperative bladder dysfunction ( p = 0.12 ) , total anastomotic leak rate ( p = 0.56 ) , and anastomotic leaks requiring reoperation ( p = 0.56 ) could be demonstrated . Conclusion Neoadjuvant chemoradiotherapy for rectal carcinoma does not increase the risk for anastomotic leakage or postoperative bladder dysfunction after curatively intended sphincter-preserving rectal resection BACKGROUND Although several authors have demonstrated that laparoscopic total mesorectal excision ( TME ) is feasible , safe , and has short-term benefits over open surgery , evidence about oncological outcome is lacking . Preoperative chemoradiation has been shown to improve local control in locally advanced rectal cancer . Therefore , neoadjuvant treatment followed by laparoscopic TME has become widely used . We review ed our series of laparoscopic TME focusing on comparison between preoperative chemoradiation therapy and primary surgery . METHODS Out of 59 patients who underwent laparoscopic TME , 20 were su bmi tted to neoadjuvant chemoradiation and represent study population . Twenty-six patients with non-metastatic rectal cancer > T1 on pathologic TNM staging who underwent primary laparoscopic surgery were considered for comparison . RESULTS No significant differences were found in operative time , in conversions to open surgery , in intra- and postoperative complications , and in anastomotic leakage rate between the two groups . No isolated local recurrence nor port-site metastases were detected in either group . Cumulative 3-year and 5-year survivals are also similar . CONCLUSION Neoadjuvant treatment does not seem to jeopardize perioperative results of laparoscopic TME . The low incidence of local recurrence reported in both groups may be attributed to a more precise dissection allowed by the endoscopic view . Laparoscopic TME and preoperative chemoradiotherapy may significantly improve oncologic results and quality of life in patients with mid and low rectal cancer . Results should be vali date d by r and omized trials with adequate follow-up BACKGROUND Survival rates after surgery for rectal cancer remain at about 40 % at 5 years from diagnosis . The aim of this study was to find out whether local recurrence rate could be reduced and survival increased by a moderately high dose of preoperative radiotherapy in patients with locally advanced , but otherwise operable , carcinoma of the rectum . METHODS We carried out a prospect i ve r and omised trial of surgery alone ( n = 140 ) versus surgery preceded by 40 Gy radiotherapy ( n = 139 ) given in 20 fractions of 2 Gy over 4 weeks . The patients , from 20 regional centres throughout the UK , were enrolled between 1981 and 1989 , and followed up for a minimum of 5 years or to death . FINDINGS 217 patients died , 114 of 140 allocated surgery alone and 103 of 139 allocated preoperative radiotherapy : median survival times were 24 months and 31 months , respectively . The hazard ratio for overall survival was 0.79 ( 95 % CI 0.60 - 1.04 , p = 0.10 ) . At 5 years ' follow-up 65 patients allocated surgery alone and 50 who received preoperative radiotherapy had local recurrence ( hazard ratio 0.68 [ 0.47 - 0.98 ] , p = 0.04 ) ; the corresponding numbers of patients with distant recurrence were 67 and 49 ( hazard ratio 0.66 [ 0.46 - 0.95 ] , p = 0.02 ) . There was a significant benefit of radiotherapy on disease-free survival ( hazard ratio 0.76 [ 0.58 - 1.0 ] , p = 0.05 ) . There was no increase in postoperative or late complications in the radiotherapy group . INTERPRETATION Our results provide further evidence that preoperative radiotherapy can reduce the rate of local recurrence of rectal cancer in patients with locally advanced disease . However , survival results are still equivocal , and so we must await the results of a meta- analysis of all radiotherapy trials from which precise and definitive results , particularly for survival , may be obtained Objective : The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival . Summary Background Data : There are many known prognostic indicators following surgery for colorectal cancer ( CRC ) . However , the impact of anastomotic leakage has not been adequately assessed . Methods : Consecutive patients undergoing resection between 1971 and 1999 were recorded prospect ively in the Concord Hospital CRC data base . Total anastomotic leakage was defined as any leak , whether local , general , or radiologically diagnosed . Patients were followed until death or to December 31 , 2002 . The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival . Confidence intervals ( CI ) were set at the 95 % level . Results : From an initial 2980 patients , 1722 remained after exclusions . The total leak rate was 5.1 % ( CI 4.1–6.2 % ) . In patients with a leak , the 5-year overall survival rate was 44.3 % ( CI 33.5–54.6 % ) compared to 64.0 % ( CI 61.5–66.3 % ) in those without leak . In proportional hazards regression – after adjustment for age , gender , urgent resection , site , size , stage , grade , venous invasion , apical node metastasis and serosal surface involvement – anastomotic leakage had an independent negative association with overall survival ( hazard ratio [ HR ] 1.6 , CI 1.2–2.0 ) and cancer-specific survival ( HR 1.8 , CI 1.2–2.6 ) . Conclusion : Apart from its immediate clinical consequences , anastomotic leakage also has an independent negative association with survival PURPOSE Total mesorectal excision ( TME ) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies . Reports on improved local control after preoperative , hypofractionated radiotherapy ( RT ) have led to the introduction of a prospect i ve r and omized multicenter trial , in which the effect of TME surgery with or without preoperative RT were evaluated . Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term . The present study was undertaken to assess the acute side effects of short-term , preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters , postoperative morbidity and mortality in patients r and omized in the Dutch TME trial . PATIENTS AND METHODS We analyzed 1,530 Dutch patients entered onto a prospect i ve r and omized trial , comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone , of which 1,414 patients were assessable . Toxicity from RT , surgery characteristics , and postoperative complications and mortality were compared . RESULTS Toxicity during RT hardly occurred . Irradiated patients had 100 mL more blood loss during the operation ( P < .001 ) and showed more perineal complications ( P = .008 ) in cases of abdominoperineal resection . The total number of complications was slightly increased in the irradiated group ( P = .008 ) . No difference was observed in postoperative mortality ( 4.0 % v 3.3 % ) or in the number of re interventions . CONCLUSION Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery , despite a slight increase in complications when compared with TME surgery only INTRODUCTION Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy . Prolongation of the interval between preoperative combined modality therapy and surgery ( RT-surgery interval ) as a means of increasing pathologic complete response rate has not been fully examined . METHODS One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified . All patients had endorectal ultrasound prior to combined modality therapy . Final pathology reports were review ed for ypT and ypN stage and margin status . Medical records were review ed for sphincter preservation , operative time , estimated blood loss , hospital stay , and morbidity ( overall , anastomotic , and perineal ) . RESULTS A pathologic complete response ( ypT0N0 ) occurred in 24 patients ( 15 percent ) . Median RT-surgery interval was 44 ( range , 15 - 206 ) days . A pathologic complete response occurred in 19 percent of patients with an interval > 44 days , vs. 12 percent in those with an interval ≤44 days ( P = 0.27 ) . Downstaging by three stages occurred more frequently in the long-interval group ( 15 percent vs. 6 percent , P = 0.11 ) . The rates of sphincter preservation , positive margins , estimated blood loss , and operative time were not significantly different . Overall morbidity was similar between groups . CONCLUSIONS Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval . However , sphincter preservation is not increased . Until prospect i ve analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome , the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear BACKGROUND The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision ( TME ) . Long-term results are reported after a median follow-up of 12 years . METHODS Between Jan 12 , 1996 , and Dec 31 , 1999 , 1861 patients with resectable rectal cancer without evidence of distant disease were r and omly assigned to TME preceded by 5 × 5 Gy radiotherapy or TME alone ( ratio 1:1 ) . R and omisation was based on permuted blocks of six with stratification according to centre and expected type of surgery . The primary endpoint was local recurrence , analysed for all eligible patients who underwent a macroscopically complete local resection . FINDINGS 10-year cumulative incidence of local recurrence was 5 % in the group assigned to radiotherapy and surgery and 11 % in the surgery-alone group ( p<0·0001 ) . The effect of radiotherapy became stronger as the distance from the anal verge increased . However , when patients with a positive circumferential resection margin were excluded , the relation between distance from the anal verge and the effect of radiotherapy disappeared . Patients assigned to radiotherapy had a lower overall recurrence and when operated with a negative circumferential resection margin , cancer-specific survival was higher . Overall survival did not differ between groups . For patients with TNM stage III cancer with a negative circumferential resection margin , 10-year survival was 50 % in the preoperative radiotherapy group versus 40 % in the surgery-alone group ( p=0·032 ) . INTERPRETATION For all eligible patients , preoperative short-term radiotherapy reduced 10-year local recurrence by more than 50 % relative to surgery alone without an overall survival benefit . For patients with a negative resection margin , the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival , which was nullified by an increase in other causes of death , result ing in an equal overall survival . Nevertheless , preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and TNM stage III . Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains . FUNDING The Dutch Cancer Society , the Dutch National Health Council , and the Swedish Cancer Society Background and Aims : In a r and omized trial the effect of short-term preoperative radio therapy and postoperative chemotherapy was studied in patients undergoing total mesorectal excision ( TME ) for clinical ly resectable rectal cancer . The primary endpoint was overall survival . The secondary endpoints published herein were the incidence of postoperative complications and adverse events with perioperative adjuvant therapy . Material and Methods : In 1995–2002 , 278 eligible patients with stage II and stage III rectal cancer were r and omly assigned to TME alone ( surgery group ) or to preoperative 25Gy radiotherapy in 5 fractions and postoperative 5-fluorouracil and leucovorin chemotherapy in addition ( RT+CTgroup ) . Results : Anastomotic leakage rate did not significantly differ between the surgery and the RT + CT group , 20.6 % vs. 27.4 % . Postoperative infections ( 15.5 vs. 26.2 % , p = 0.037 ) and perineal wound dehiscence ( 15.9 vs. 38.5 % , p = 0.045 ) were more common after radiotherapy . Grade 3–5 adverse events were uncommon with preoperative radiotherapy ( one , 0.7 % with reversible lumbar plexopathy ) and postoperative chemotherapy ( hematologic in 10.8 % , with one septic death , and gastrointestinal in 4.8 % ) . Conclusions : Perioperative adjuvant therapy was generally well tolerated and did not lead to an increase in serious surgical complications . Wound infections and perineal wound dehiscence were more common in irradiated patients |
439 | 23,666,096 | Identified facilitators suggest that the quality of rounds is improved when conducted by a multidisciplinary group of providers , with explicitly defined roles , using a st and ardized structure and goal -oriented approach that includes a best practice s checklist .
Barriers to quality patient care rounds include poor information retrieval and documentation , interruptions , long rounding times , and allied healthcare provider perceptions of not being valued by rounding physicians . | OBJECTIVES Patient care rounds are a key mechanism by which healthcare providers communicate and make patient care decisions in the ICU but no synthesis of best practice s for rounds currently exists .
Therefore , we systematic ally review ed the evidence for facilitators and barriers to patient care rounds in the ICU . | Background Clinical h and over is a necessary process for the continuation of safe patient care ; however , deficiencies in the h and over process can introduce error . While the number of h and over studies increases , few have vali date d implemented improvements with repeated audit . Objective To improve the morning h and over round on a busy critical care unit and assess sustainability of improvement through repeated audit . Design / Methods A quality improvement process based on prospect i ve observational assessment of the doctor 's shift-change h and over was carried out , assessing the content of clinical information and effects of distractions , location and timing . The effect of a training session for the junior doctors with the introduction of a st and ardised h and over protocol was assessed . Results The content of clinical information improved after the training session with introduction of a st and ardised protocol , but returned to baseline with a new cohort of untrained doctors . Distractions were associated with increased h and over times for individual patients and for total h and over time . Overall , h and over time was shortest in the coffee room compared with ward and lecture theatre h and overs . Individual patient h and over time was positively correlated with clinical content scores . Four indices of critical illness all positively correlated with increased h and over time . Conclusions Early specific training is vital for quality clinical h and over . Distractions during h and over cause inefficiency and can adversely affect information transfer . Changing h and over location according to local environment can yield improved efficiency , structure and ease of management . Adequate time must be allocated for clinical h and over especially when dealing with very sick and complex patients A critical care clinical pharmacy specialist was assigned to the burn center to make scheduled rounds with the physicians and to attend the weekly multidisciplinary burn team rounds . A prospect i ve 6-month study was completed to 1 ) determine the clinical impact of the pharmacist 's interventions and 2 ) quantify cost savings generated by these interventions . Prospect i ve data concerning clinical interventions by the pharmacist were collected during a 6-month period . Each intervention was independently review ed by two attending burn surgeons to determine its importance . A total of 165 interventions in 76 patients were documented . Following an independent review of each intervention by burn surgery attendings , 121 of 165 interventions were felt to have improved overall patient care , 42 of 165 prevented possible drug-related toxicity or organ dysfunction , 1 of 165 prevented a possible life-threatening event , and only 1 of 165 was considered insignificant . Drug changes suggested by the pharmacist result ed in a savings of $ 11,081.14 for the 6-month period . The integration of the critical care pharmacist into clinical rounds results in significant cost avoidance and improves overall patient care CONTEXT Pharmacist review of medication orders in the intensive care unit ( ICU ) has been shown to prevent errors , and pharmacist consultation has reduced drug costs . However , whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied . OBJECTIVE To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events ( ADEs ) caused by ordering errors . DESIGN Before-after comparison between phase 1 ( baseline ) and phase 2 ( after intervention implemented ) and phase 2 comparison with a control unit that did not receive the intervention . SETTING A medical ICU ( study unit ) and a coronary care unit ( control unit ) in a large urban teaching hospital . PATIENTS Seventy-five patients r and omly selected from each of 3 groups : all admissions to the study unit from February 1 , 1993 , through July 31 , 1993 ( baseline ) and all admissions to the study unit ( postintervention ) and control unit from October 1 , 1994 , through July 7 , 1995 . In addition , 50 patients were selected at r and om from the control unit during the baseline period . INTERVENTION A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning , and was available on call throughout the day . MAIN OUTCOME MEASURES Preventable ADEs due to ordering ( prescribing ) errors and the number , type , and acceptance of interventions made by the pharmacist . Preventable ADEs were identified by review of medical records of the r and omly selected patients during both preintervention and postintervention phases . Pharmacists recorded all recommendations , which were then analyzed by type and acceptance . RESULTS The rate of preventable ordering ADEs decreased by 66 % from 10.4 per 1000 patient-days ( 95 % confidence interval [ CI ] , 7 - 14 ) before the intervention to 3.5 ( 95 % CI , 1 - 5 ; P<.001 ) after the intervention . In the control unit , the rate was essentially unchanged during the same time periods : 10.9 ( 95 % CI , 6 - 16 ) and 12.4 ( 95 % CI , 8 - 17 ) per 1000 patient-days . The pharmacist made 366 recommendations related to drug ordering , of which 362 ( 99 % ) were accepted by physicians . CONCLUSIONS The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors . Nearly all the changes were readily accepted by physicians OBJECTIVE To evaluate the clinical pharmacists ' interventions in an intensive care unit ( ICU ) setting with regard to their acceptance by the medical team , frequency , clinical significance , and targeted patient 's outcomes . METHODS This is a prospect i ve , non-comparative , observational study evaluating the clinical pharmacist interventions in an ICU setting from December 2002 to May 2003 . The study was conducted in a 19-bed Cardiac-Surgery ICU at King Faisal Specialist Hospital & Research Center , a tertiary-care hospital in Riyadh , Saudi Arabia . The clinical pharmacist performed daily multi-disciplinary team rounds , with documentation of all his interventions . On the same day , a physician , who is a part of the team , verified all interventions for validity and clinical significance . The institutional Office of Research Affairs approved the study . RESULTS The clinical pharmacist intervened 394 times on the 600 patients [ 0.66 intervention-per-patient ] . The medical team accepted almost all interventions ( 94.3 % ) . The main drug-related problems were the following : no drug prescribed for medical condition ( 33.2 % ) , inappropriate dosing regimen ( 28.9 % ) , and no indication for drug use ( 14.3 % ) . Approximately 55.7 % of the interventions targeted enhancing therapeutic outcomes , whilst 21.8 % of interventions result ed in the prevention of an adverse drug reaction . The interventions that may have result ed in decreasing mortality , preventing , or reducing organ damage , or decreasing hospitalization , represented 8.1 % of all interventions . CONCLUSION Participation of a clinical pharmacist in the daily multidisciplinary team rounds in an ICU setting significantly reduces unfavorable morbidities and enhances therapeutic outcomes We prospect ively studied the relationship between interdisciplinary collaboration and patient outcomes in the medical intensive care unit ( MICU ) using nurses ' and residents ' reports of amount of collaboration involved in making decisions about transferring patients from the MICU to a unit with a less intense level of care . Either readmission to the MICU or death was considered a negative patient outcome . Nurses ' reports of collaboration were significantly ( p = 0.02 ) and positively associated with patient outcome , controlling for severity of illness . Patient predicted risk of negative outcome decreased from 16 % , when the nurse reported no collaboration in decision making , to 5 % when the process was fully collaborative . There was an interaction of collaboration with availability of alternative choices in the transfer decision-making situation . When alternatives were available , collaboration was more strongly associated with patient outcome . There was no significant relationship between residents ' reports of collaboration and patient outcomes . The correlation between amount of collaboration reported by nurses and residents about the same decisions was quite low ( r = 0.10 ) BACKGROUND The Joint Commission on the Accreditation of Healthcare Organizations reports that communication breakdowns are responsible for 85 % of sentinel events in hospitals . Patients in surgical ICUs are the most vulnerable to communication errors . Fellows and residents are an integral part of the surgical ICU team , but little is known about resident-fellow communication and its impact on surgical ICU patient outcomes . The objective of this study is to describe resident-fellow patient care communication patterns in the surgical ICU and correlate established communication patterns with short-term outcomes . STUDY DESIGN A prospect i ve observational trial was conducted for 136 consecutive surgical ICU days . We evaluated resident-fellow communication of four cardiorespiratory events : hypotension , new arrhythmias , tachypnea , and desaturation . We prospect ively defined three short-term outcomes : improved , not improved , and worse . An intervention was attempted to improve communication . RESULTS Three hundred twelve events were collected ( 166 observational and 146 interventional ) . PGY3 residents covered approximately 60 % of days in both phases . PGY3 residents were responsible for 73 % of communication errors in the observational phase and 59 % of communication errors in the interventional phase . Communication errors were more likely in the late shift ( p < 0.0001 ) . The late shift was responsible for 77 % of all communication errors . Communication errors result ed in worse short-term outcomes for cardiorespiratory events ( p < 0.0002 ) . Effective communication was a significant predictor of improved short-term outcomes ( p < 0.0003 ) . The intervention decreased communication errors in the late shift by 10 % ( p < 0.052 ) . CONCLUSIONS Communication errors occurred more frequently during the late shift . These communication errors were associated with worsened short-term outcomes . Improved communication in the surgical ICU is a fruitful target to improve clinical outcomes Objective : To improve communication during daily rounds using sequential interventions . Design : Prospect i ve cohort study . Setting : Multidisciplinary pediatric intensive care unit in a university hospital . Subjects : The multidisciplinary rounding team in the pediatric intensive care unit , including attending physicians , physician trainees , and nurses . Interventions : Daily rounds on 736 patients were observed over a 9-month period . Sequential interventions were timed 8–12 wks apart : 1 ) implementing a new resident daily progress note format ; 2 ) creating a performance improvement “ dashboard ” ; and 3 ) documenting patients ' daily goals on bedside whiteboards . Measurements and Main Results : After all interventions , team agreement with the attending physician 's stated daily goals increased from 56.9 % to 82.7 % ( p < .0001 ) . Mean agreement increased for each provider category : 65.2 % to 88.8 % for fellows ( p < .0001 ) , 55.0 % to 83.8 % for residents ( p < .0001 ) , and 54.1 % to 77.4 % for nurses ( p < .0001 ) . In addition , significant improvements were noted in provider behaviors after interventions . Barriers to communication ( bedside nurse multitasking during rounds , interruptions during patient presentations , and group disassociation ) were reduced , and the use of communication facilitators ( review of the prior day 's goals , inclusion of bedside nurse input , and order read-back ) increased . The percentage of providers reporting being “ very satisfied ” or “ satisfied ” with rounds increased from 42.6 % to 78.3 % ( p < .0001 ) . Conclusions : Shared agreement of patients ' daily goals among key healthcare providers can be increased through process-oriented interventions . Improved agreement will potentially lead to improved quality of patient care and reduced medical errors BACKGROUND The incidence of ventilator-associated pneumonia ( VAP ) in trauma patients can be decreased with use of the ventilator bundle ( VAPB ) . Our VAP rate remained high despite the adoption of the VAPB . To better implement the VAPB , a multidisciplinary team composed of the surgical intensive care unit ( SICU ) nursing staff , physician , and respiratory therapist review ed briefly a checklist of VAPB goals for each patient before morning attending rounds . We hypothesized that such daily goal rounds ( GR ) focused on the VAPB would decrease the VAP rate . METHODS A pre-GR ten-month period ( November 2006 to August 2007 ) was compared with the ten-month period ( September 2007 to June 2008 ) with daily GRs . The occurrence of VAPs was tallied prospect ively in all intubated trauma patients using the National Nosocomial Infection Surveillance criteria . Patient characteristics and outcome data were obtained from our trauma registry and medical records . Patient characteristics were similar in the 85 pre-GR patients and the 89 GR patients . RESULTS The number of VAPs decreased 67 % in the GR patients ( 15 pre-GR vs. 5 GR ; p=0.02 ) ; however , the all-cause mortality rate remained similar ( 16.5 % vs. 21.3 % ; p=0.41 ) . When patients were divided into those with and without VAP , there was a significant increase in mean ventilator , SICU , and hospital days in patients with VAP ( p=0.01 for all ) . There were only two deaths among trauma patients with VAP . CONCLUSION Daily multidisciplinary GRs focused on the VAPB can decrease the incidence of VAP significantly in trauma patients . Ventilator-associated pneumonia correlated with extended mean ventilator , SICU , and hospital days . Interestingly , despite a significant decrease in VAP , a decrease in the mortality rate was not observed . Given the small number of deaths in the VAP cohort , this study has insufficient statistical power to eluci date the true impact of GR intervention or VAP on the mortality rate in trauma patients OBJECTIVE To assess the impact of the implementation of a daily goals sheet upon nursing perception of communication in an academic , tertiary care paediatric intensive care unit ( PICU ) . DESIGN Prospect i ve , longitudinal , before- and -after intervention surveys . SETTING University affiliated 12-bed PICU . SUBJECTS Bedside nurses . INTERVENTIONS A question naire was administered to PICU nurses addressing their perception of communication . Following this question naire , the use of a daily goals sheet was instituted . A second question naire was administered one year later . Mann-Whitney Rank Sum Test was used to compare differences of the grade d outcome variables . MEASUREMENTS AND MAIN RESULTS The primary outcome was the perception of communication taken from a nursing perspective . Eighty-five percent of nurses felt the daily goals sheet led to improved communication between physicians and nurses in the PICU . All questions related to communication demonstrated a positive influence of the goals sheet , with the perception of the PICU staff working as a team reaching statistical significance ( p=0.05 ) . The perception of the care of one surgical service being attending physician directed also significantly improved after the institution of the goals sheet ( p=0.04 ) . CONCLUSION The institution of a daily goals sheet led to an improvement in nursing perception of communication . Future studies are required to determine if this change in process has a demonstrable effect on health care outcomes of critically ill children , or whether this tool can have the same beneficial effects in other academic and non-academic PICUs OBJECTIVE Research ers have no empirically based search stopping rule when looking for potentially relevant articles for inclusion in systematic review s. We tested a stopping strategy based on capture-mark-recapture ( CMR ; i.e. , the Horizon Estimate ) statistical modeling to estimate the total number of articles in the domain of clinical decision support tools for osteoporosis disease management using four large bibliographic data bases ( Medline , EMBASE , CINAHL , and EBM review s ) . STUDY DESIGN AND SETTING Retrospective evaluation of the Horizon Estimate using a systematic review of r and omized controlled trials ( RCTs ) at two levels of article screening : title and abstract ( 1,246 potentially relevant articles ) and full text ( 42 potentially relevant articles ) . RESULTS The CMR model suggests that the total number of potential articles was 1,838 for the first level of screening , and 49 for the full-text level . The four data bases provided 68 % of known articles for the first level of screening and 81 % for full-text screening . CONCLUSIONS The CMR technique can be used in systematic review s to estimate the closeness to capturing the total body of literature on a given topic . More studies are needed to objective ly determine the usefulness of Horizon Estimates as a stopping rule strategy for systematic review search ing BACKGROUND Clear communication is imperative if teams in any industry expect to make improvements . An estimated 85 % of errors across industries result from communication failures . PURPOSE The purpose of this study was to evaluate and improve the effectiveness of communication during patient care rounds in the intensive care unit ( ICU ) using a daily goals form . DESIGN We conducted a prospect i ve cohort study in collaboration with the Volunteer Hospital Association ( VHA ) , Institute for Healthcare Improvement ( IHI ) , and Johns Hopkins Hospital 's ( JHH ) 16-bed surgical oncology ICU . All patients admitted to the ICU were eligible . Main outcome variables were ICU length of stay ( LOS ) and percent of ICU residents and nurses who understood the goals of care for patients in the ICU . Baseline measurements were compared with measurements of underst and ing after implementation of a daily goals form . RESULTS At baseline , less than 10 % of residents and nurses understood the goals of care for the day . After implementing the daily goals form , greater than 95 % of nurses and residents understood the goals of care for the day . After implementation of the daily goals form , ICU LOS decreased from a mean of 2.2 days to 1.1 days . CONCLUSION Implementing the daily goals form result ed in a significant improvement in the percent of residents and nurses who understood the goals of care for the day and a reduction in ICU LOS . The use of the daily goals form has broad applicability in acute care medicine Objective : There are few investigations evaluating the impact of physician management and leadership skills on patient care . Our objective was to determine whether there were perceived differences in management and leadership performance within a group of intensivists and to correlate these differences with processes of care outcomes . Design : Prospect i ve cohort from January 31 to June 30 , 2005 . Setting : Pediatric intensive care unit in an urban , academic children 's hospital . Participants : Pediatric intensive care unit staff intensivists were the primary participants . Interventions : None . Measurements and Main Results : The intensivists ' management and leadership performances were assessed by residents and fellows using the Physician Management Index . The primary outcome attributable to the staff was the accomplishment of daily patient goals . A total of 827 resident and fellow assessment s of the management and leadership performance of attendings ( n = 8) were collected over 2077 patient days ( 103.4 ± 39.0 surveys/attending ) . The mean Physician Management Index was 78.1 ± 6.2 and differed significantly among the attendings ( p < .001 ) . There was excellent agreement by the raters concerning attending performance ( intraclass correlation = 0.801 ) . The attendings ' Physician Management Indexes were correlated with age ( r = 0.594 , p < .001 ) and experience ( r = 0.656 , p < .001 ) but not other personal or environmental factors . An average of 3.3 ± 0.6 goals per patient were written each day , and 86.0 % ± 7.0 % were accomplished . Accomplishment of patient goals was correlated with the Physician Management Index ( r = 0.306 , p < .001 ) and length of rounds ( r = −0.341 , p < .001 ) . Other variables , including midnight census , numbers of admissions and discharges , codes , and consultations , did not correlate with the Physician Management Index . Conclusions : Management and leadership performance of attending intensivists can be measured and is associated with efficiency of care as assessed by accomplishment of daily patient goals . Attendings differ in their management and leadership performances STUDY OBJECTIVE The aim of the study was to evaluate the impact of prospect i ve review of significant drug-drug interactions ( DDIs ) occurring in medical intensive care unit ( MICU ) patients by the critical care pharmacist participating in patient care rounds on improvement of safer and more efficacious medication use . STUDY DESIGN A prospect i ve consecutive 10-week study was conducted in the MICU , St Luke's/Roosevelt Hospital Center ( St Luke 's site ) , New York , NY . This study compared baseline period when clinical pharmacist services were not provided with the period when each patient 's profile was review ed daily during MICU rounds and interactions were minimized . The study examined whether the presence of critical care pharmacist would decrease the number of significant DDIs in the MICU . Impact of decreasing presence of severe DDIs on length of stay ( LOS ) and discharge status was also evaluated . RESULTS Having a pharmacist on rounds result ed in statistically significant decrease in number of clinical ly important interactions requiring therapy modification , rated D-X ( Poisson regression B = -1.036 ; 95 % confidence interval , -1.318 to -0.753 ; P < .01 ) . The coefficient ( -1.036 ) indicates the incidence rate ratio of 0.35 , meaning that the presence of clinical pharmacist in MICU rounds decreased DDI rate by 65 % . According to the multiple linear regression , lower number of DDIs was associated with shorter LOS ( P < .01 ) . Inpatient mortality rate was lower in the intervention group compared with the preintervention group . Number of DDIs was not significantly associated with mortality based on simple regression ( P = .45 ) or multiple regression analysis ( P = .09 ) . CONCLUSION Implementing a DDI screening procedure results in significantly lower number of important DDI in the MICU and shortens LOS OBJECTIVE The use of " care bundles " in the prevention of ventilator-associated pneumonia ( VAP ) and other intensive care unit ( ICU ) complications have been increasingly used in critical care practice . However , the effective implementation of these strategies represents a challenge in a busy Level I trauma ICU . We devised a daily " Quality Rounds Checklist " ( QRC ) tool for use in the ICU to increase compliance with these prophylactic measures and identify areas for improvement in quality of care . METHODS A prospect i ve before-after design was used to examine the effectiveness of the QRC tool in promoting compliance with 16 prophylactic measures for VAP , deep venous thrombosis or pulmonary embolism , central line infection and other ICU complications . Compliance was assessed for 1 month before institution of the QRC . On daily analysis , the QRC was then applied by the ICU fellow to assess compliance . Any deficiencies were actively corrected in real time . Compliance was assessed by a multidisciplinary team for the next 3 months and compared with the pre-QRC compliance rates . RESULTS Implementation of the QRC tool facilitated improvement of all measures not already at > 95 % compliance . Compliance with VAP prevention measures of head of bed elevation > 30 degrees ( 35.2 % vs. 84.5 % ) , sedation holiday ( 78.0 % vs. 86.0 % ) , and prophylaxis for both peptic ulcer disease ( 76.2 % vs. 92.3 % ) and deep venous thrombosis ( 91.4 % vs. 92.8 % ) were all increased . A decrease in central line duration > 72 hours ( 62.4 % vs. 52.8 % ) and ventilator duration > 72 hours ( 74.0 % vs. 61.7 % ) was also noted . Additionally , a decrease in mean monthly rates per 1,000 device days of VAP ( 16.3 vs. 8.9 ) , central line infection ( 11.3 vs. 5.8 ) and self-extubation ( 7.8 vs. 2.2 ) was demonstrated . CONCLUSION Introducing a daily QRC tool facilitated improved compliance rates for 16 clinical ly significant prophylactic measures in a busy Level I trauma ICU . The daily use of this tool , requiring just a few minutes per patient to complete , results in a sustainable improvement in patient outcomes OBJECTIVES . Case presentation and teaching performed at the bedside are declining . Patients ' preference between bedside case presentation and conference-room case presentation is divergent in the literature . Residents seem to prefer the conference room . The objective of this study was to ascertain whether there was a difference of satisfaction and comfort between bedside case presentation and conference-room case presentation for the parents of patients hospitalized in the PICU and for the residents in training in the PICU . METHODS . Every child hospitalized in the PICU who had 2 consecutive morning rounds , performed in the presence of the same resident , attending pediatrician , and parent , was eligible for the study . The study began with the first patient 's case presentation after admission in the PICU . R and omization was on the first case presentation : bedside or conference room . On the second day , the other type of case presentation was performed . After each round , the parents and the resident filled out a question naire . RESULTS . Twenty-seven parents of 22 patients answered both question naires , and 21 question naires were answered by residents . Parents ' satisfaction was significantly higher during bedside case presentation ( 96 vs 92 , answers reported on a 100-mm linear scale ) , they preferred bedside case presentation ( 95 vs 15 ) , and they were more comfortable attending bedside teaching ( 89 vs 19 ) . There was no difference in the residents ' satisfaction nor in their comfort giving the actual case presentation . Residents , on the other h and , were significantly more comfortable asking questions ( 84 vs 69 ) and being asked questions ( 85 vs 67 ) during conference-room case presentation . A total of 81 % of the parents wished that the next case presentation would take place at the bedside . CONCLUSIONS . This study demonstrates the feasibility of a clinical case presentation performed at the bedside in the PICU context that seems to satisfy parents without causing too much discomfort to residents . Thus , bedside case presentation could be a very good teaching strategy in university hospitals |
440 | 31,119,554 | The trial sequential analysis suggested that there is adequate evidence supporting the efficacy of topical magnesium in preventing postoperative sore throat .
Conclusion Our study suggests that preoperative topical magnesium can effectively prevent postoperative sore throat .
ConclusionS elon les résultats de notre étude , l’application préopératoire topique de magnésium est efficace pour prévenir les maux de gorge postopératoires . | Background Postoperative sore throat negatively affects patient satisfaction and recovery .
We conducted a systematic review and meta- analysis to examine the efficacy of preoperative topical administration of magnesium sulfate in preventing postoperative sore throat in adult patients .
Trial registration PROSPERO ( CRD42018110019 ) ; registered 26 September , 2018.Résumé Context eLes maux de gorge postopératoires ont un impact négatif sur la satisfaction et la récupération des patients .
Nous avons réalisé une revue systématique et une méta-analyse afin d’examiner l’efficacité d’une administration topique préopératoire de sulfate de magnésium pour prévenir les maux de gorge postopératoires chez les patients adultes . | 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 and objective : Sore throat and hoarseness rank , besides pain and nausea , among the most frequent subjective complaints after tracheal intubation for general anaesthesia . Our intention was to determine the incidence of postoperative sore throat from a large sample of patients and thus to identify the most important associated factors . Methods : We prospect ively followed up 809 adult patients who underwent elective surgical interventions and examined their history , the applied anaesthetic techniques , perioperative course and the occurrence , intensity and duration of postoperative throat complaints . The assignment and professional experience of the involved intubators were also assessed . The influence of a multitude of variables on postoperative throat complaints was statistically analysed . Results : Postoperative sore throat was present in 40 % overall being significantly higher in female than in male ( 44 % vs. 33 % ; P = 0.001 ) . The mean pain intensity in the affected patients ( n = 323 ) was 28 ± 12 mm on a visual analogue scale where 0 = no pain and 100 = extreme pain . The average duration was 16 ± 11 h. Main factors associated with throat complaints were female sex , history of smoking or lung disease , duration of anaesthesia , postoperative nausea , bloodstain on the endotracheal tube and natural teeth . We could find no influence on the occurrence or intensity of throat complaints by the professional assignment or the length of professional experience of the personnel involved . Conclusions : Postoperative throat complaints frequently arise after tracheal intubation for general anaesthesia in the first 2 postoperative days , but they are of limited intensity and duration Background and Aims : Postoperative sore throat ( POST ) is a well-recognized complication after general anesthesia ( GA ) . Numerous nonpharmacological and pharmacological measures have been used for attenuating POST with variable success . The present study was conducted to compare the efficiency of preoperative nebulization of normal saline and magnesium sulfate in reducing the incidence of POST following GA . Material s and Methods : Following institutional ethical committee approval and written informed consent , a prospect i ve r and omized double-blinded study was conducted in 100 cases divided into two equal groups . Patients included in the study were of either gender belonging to American Society of Anesthesiologist ( ASA ) status 1 or 2 undergoing elective surgery of approximately 2 h or more duration requiring tracheal intubation . Patients in Group A are nebulized with 3 ml of normal saline and the patients in Group B are nebulized with 3 ml of 225 mg isotonic nebulized magnesium sulfate for 15 min , 5 min before induction of anesthesia . The incidence of POST at rest and on swallowing and any undue complaints at 0 , 2 , 4 , and 24 h in the postoperative period are evaluated . Results : There is no significant difference in POST at rest during 0th , 2nd and 4th h between normal saline and MgSO4 . Significant difference is seen at 24th h , where MgSO4 lessens POST . There is no significant difference in POST on swallowing during 0th and 2nd h between normal saline and MgSO4 . Significant difference is seen at 4th h , where MgSO4 has been shown to lessen POST . Conclusions : MgSO4 significantly reduces the incidence of POST compared to normal saline BACKGROUND Postoperative sore throat is a common complication of anaesthesia and can lead to dissatisfaction after surgery . Many factors can contribute to postoperative sore throat and the incidence varies with the method of airway management . METHODS In this prospect i ve observational study elective gynaecological and general surgical patients were interviewed 24 hours postoperatively to determine the presence of sore throat . Information collected included demographic data , surgical procedure , duration of surgery , airway device used and position of patient during surgery . This study was done over a period of 3 months . RESULTS 312 patients were interviewed . 81(26 % ) patients suffered with sore throat postoperatively . 28 % of patients with endotracheal intubation ( ETT ) and 3.5 % of patients with laryngeal mask airway had a sore throat . Female patients reported more sore throat than male patients ( 27.1 % vs. 19.1 % ) . Sore throat was found to be more common with older age group , grade of difficulty in intubation , duration of surgery and patient 's position during surgery . CONCLUSION Awareness of the factors responsible for increased incidence of postoperative sore throat and appropriate care especially during endotracheal intubation can help to reduce the incidence of postoperative sore throat BACKGROUND Postoperative sore throat ( POST ) has been one of the most common complaints after anesthesia . In Siriraj Hospital , a high volume of general anesthesia is performed annually , but there was limited data regarding this complaint . OBJECTIVE To describe the incidence of POST and to determine risk factors associated with the occurrence of POST MATERIAL AND METHOD : Three hundred eighty seven patients were prospect ively studied . Demographic data , airway management , and intra-operative data were recorded . Sore throat occurrence and its intensity at postoperative 24 hours as well as patient satisfaction were assessed . RESULTS The overall incidence of POST was 35.7 % ( 95 % confidence interval [ CI ] 30.9 - 40 . 7 % ) with the mean intensity of 29.8 + /- 21.2 . Operation of the neck was found to be an independent risk factor of 24-hour POST ( odds ration [ OR ] 3.43 , 95 % confidence interval [ CI ] 1.88 - 6.25 , p < 0.001 ) , whereas in gynecological surgery the occurrence was significantly attenuated ( OR 0.49 , 95 % CI 0.26 - 0.95 , p = 0.035 ) . CONCLUSION POST was common after general anesthesia . Careful airway management might be the key to prevent this occurrence and to improve the quality of anesthetic care Background Diffusion of nitrous oxide into the cuff of the endotracheal tube results in an increase in cuff pressure . Excessive endotracheal tube cuff pressure may impair tracheal mucosal perfusion and cause tracheal damage and sore throat . Filling the cuff of the endotracheal tube with saline instead of air prevents the increase in cuff pressure due to nitrous oxide diffusion . This method was used to test whether tracheal morbidity is related to excess in tracheal cuff pressure during balanced anesthesia . Methods Fifty patients with American Society of Anesthesiologists physical status I or II were r and omly allocated to two groups with endotracheal tube cuffs initially inflated to 20–30 cm H2O with either air ( group A ) or saline ( group S ) . Anesthesia was maintained with isoflurane and nitrous oxide . At the time of extubation , a fiberoptic examination of the trachea was performed by an independent observer , and abnormalities of tracheal mucosa at the level of the cuff contact area were scored . Patients assessed their symptoms ( sore throat , dysphagia , and hoarseness ) at the time of discharge from the postanesthesia care unit and 24 h after extubation on a 101-point numerical rating scale . Results Cuff pressure increased gradually during anesthesia in group A but remained stable in group S. The incidence of sore throat was greater in group A than in group S in the postanesthesia care unit ( 76 vs. 20 % ) and 24 h after extubation ( 42 vs. 12%;P < 0.05 ) . Tracheal lesions at time of extubation were seen in all patients of group A and in eight patients ( 32 % ) of group S ( P < 0.05 ) . Conclusion Excess in endotracheal tube cuff pressure during balanced anesthesia due to nitrous oxide diffusion into this closed gas space causes sore throat that is related to tracheal mucosal erosion Context : Postoperative sore throat ( POST ) is a complication that is unresolved in patients undergoing endotracheal intubation . Aim : To compare the effects of ketamine and magnesium sulfate nebulizations in two strengths , on the incidence and severity of POST , hoarseness , and cough . Setting s and Design : Sixty surgical patients undergoing elective abdominal and lower limb surgeries under combined epidural and general anesthesia were included in this prospect i ve , r and omized , double-blinded study . Subjects and Methods : Patients in each group were nebulized with the respective study drug 15 min prior to the surgery , i.e. , ketamine in Group K , magnesium sulfate 250 mg , and 500 mg in Group M1 and Group M2 , respectively , and normal saline as control in Group C. A st and ardized anesthesia protocol was followed for all patients . After extubation , the patients were asked to grade POST , hoarseness , and cough at 0 , 2 , 4 , 12 , and 24 h. Statistical Analysis Used : One-way analysis of variance , Chi-square test , Fisher 's exact test , paired t-tests , and Wilcoxon 's signed-rank test as applicable . Results : Ketamine and magnesium sulfate 500 mg demonstrated a statistically significant decrease in POST at 0 , 2 , and 4 h , and postoperative hoarseness at 0 h. There was decrease in the incidence and severity of sore throat , hoarseness , and cough at all periods in the study groups as compared with control . Conclusion : Nebulization with ketamine 50 mg and magnesium sulfate 500 mg , 15 min before induction of general anesthesia and intubation , reduce the incidence and severity of POST and hoarseness of voice BACKGROUND Sore throat is a common complication of anaesthesia that affects patient satisfaction after surgery . METHODS We studied 5264 ambulatory surgical patients prospect ively to determine the patient , anaesthetic , and surgical factors associated with sore throat . RESULTS In 5264 patients , 12.1 % reported a sore throat . Patients with tracheal tube had the greatest incidence , 45.4 % , followed by patients with laryngeal mask airway , 17.5 % , while patients with a facemask had a lower incidence of sore throat , 3.3 % . Female patients had more sore throats than male patients ( 13.4 vs 9.1 % ) . Airway management had the strongest influence on the incidence of sore throat . Sore throat in ambulatory surgical patients was associated with female sex , younger patients , use of succinylcholine , and gynaecological surgery . CONCLUSION Airway management , female sex , younger patients , surgery for gynaecological procedure , and succinylcholine predicts postoperative sore throat . Increased awareness of the predictive factors can help to avoid this combination and improve patient satisfaction BACKGROUND Sore throat and hoarseness are common complications , but these have not been studied after total i.v . anaesthesia . METHODS We prospect ively studied 418 surgical patients , aged 15 - 92 yr , after total i.v . anaesthesia with propofol , fentanyl and ketamine to assess possible factors associated with sore throat and hoarseness . RESULT We found sore throat in 50 % and hoarseness in 55 % of patients immediately after surgery . This decreased to 25 % for sore throat and 24 % for hoarseness on the day after surgery . Both sore throat and hoarseness were more common in females and when lidocaine spray had been used . Cricoid pressure during laryngoscopy was inversely associated with the risk of sore throat . CONCLUSION Knowledge of these factors may reduce postoperative throat complications , and improve patient satisfaction S ystematic review s are relied upon by clinicians and policymakers as high- quality evidence for decision-making . In some hierarchies of evidence quality , systematic review s are ranked at the top , higher than r and omized controlled trials . A properly conducted systematic review that is based on high- quality articles provides very strong evidence ; policymakers recognize this value and solicit many such review s. Busy clinicians rely on well-executed systematic review s to quickly synthesize the literature and guide them in managing patients . However , there are important inherent weaknesses that can limit the quality of systematic review s and can lead to erroneous conclusions . Consumers of systematic review s should approach them with a healthy sense of skepticism . Unfortunately , many of these weaknesses may not be obvious to the various stakeholders who routinely invest their trust in such review s. The first bias one encounters is inherent in the research enterprise . Generally , research ers design studies to demonstrate maximum effect ; hence they are careful about the population selected , the interventions tested , and the outcomes assessed . For example , interventions are often tested in population s that are at high risk for experiencing the outcome in question and are likely to respond to the intervention . Not only can this make results difficult to generalize , but it often results in studies that overstate the benefit ; subsequent studies frequently find less benefit . This is particularly common when the pool of available studies consists of small , single-center investigations , trials that are particularly likely to show large effects . While usually not intentional , the combination of careful selection of population and outcomes can distort clinical research and obscure truth . This inherent bias in the research enterprise can not be fixed ; however , if there are a sufficient number of studies , conducted across different setting s and population s , this problem can be partially ameliorated with systematic review s. Systematic review s are vulnerable to a number of biases . First , the question may not be well-defined . A marker of a high- quality systematic review is the inclusion of a purpose statement in which the specific research question is clearly articulated . Specificity is key : what are they willing to accept as evidence , what population , what intervention , what duration , what doses , what outcomes and when ? Second , the search strategy should be broad enough to reassure readers that no studies were left out . Research ers commonly limit their search to English- language articles . However , there is no difference between the quality of articles in English and those in other language s , and limiting the search to English-only should be a red flag to readers . The bibliographies of retrieved articles should also be review ed . All search strategies should include input from an experienced medical librarian . Third , the quality of included articles must be carefully assessed . The higher the quality of articles that provide the bulk of the systematic review ’s conclusions , the more confident readers can be in those conclusions . Readers should be wary of review s that are based on observational data or uncontrolled clinical trials . A statistical package will analyze whatever data the analyst feeds it , and will provide an estimate of an overall effect and a 95 % confidence interval . This can mislead readers into believing that our underst and ing of the effect is more concrete than it is . Pooling of observational data can lead to answers that differ material ly from the results of r and omized controlled trials . Readers should also be wary of systematic review s built on low sample numbers , either few studies or small sample s within each study . The number of studies necessary to produce believable results is an area of ongoing debate . A recent article discussed the benefits of Trial Sequential Analysis ( TSA ) , a method that allows metaanalysts to determine the likelihood that the review contains either a type I error ( finding a difference that does not exist ) or a type II error ( reporting no difference when in fact one exists ) . TSA theory is similar to the principles governing stopping rules for interventional trials . It takes the total sample size and the size of the effect , and establishes boundaries . These boundaries provide confidence that the sample size is large enough to avoid type I or II errors . We strongly recommend routinely including them in meta-analyses . Fourth , very careful attention must be paid to the issue of publication bias . Most readers recognize that studies with nonsignificant results face greater publication hurdles . This is a wellrecognized phenomenon ; protocol s with non-significant results are both less likely to be published and , when published , more likely to encounter significant delays than studies with significant Published online December 12 , Background Sore throat is common after tracheal intubation . Water can be used to lubricate tracheal tubes , but its benefit has not been vali date d. We thus did a r and omised non-inferiority trial to test the hypothesis that a tube lubricated with water does not reduce sore throat after tracheal intubation . Methods We r and omized female or male patients ( n = 296 ) undergoing surgery in the ears or eyes to receive either a tube lubricated with water or a tube without lubrication for intubation . We assessed sore throat at 0 , 2 , 4 , and 24 h after surgery ; pharyngeal injury at 2 and 24 h after surgery ; and respiratory infections within 7 days after surgery . For the incidence of sore throat within 24 h after surgery ( primary outcome ) , the two-sided 90 % confidence interval of the risk difference was compared with the prespecified non-inferiority margin of 15 % . Other outcomes were analyzed with two-sided superiority tests . Results The incidence of sore throat within 24 h after surgery was 80/147 ( 54.4 % ) in the non-lubricated tube group and 83/149 ( 55.7 % ) in the water-lubricated tube group ( risk difference -1.3 % , 90 % confidence interval -10.9 % to 8.3 % ) . Because the confidence interval was below the non-inferiority margin , the incidence of sore throat was not higher in the non-lubricated tube group than in the water-lubricated tube group . There was no significant association between groups in the sore throat , pharyngeal injury , and respiratory infection at each assessment time . Conclusions The tube lubricated with water did not reduce sore throat and pharyngeal injury after tracheal intubation compared to the tube without lubrication |
441 | 31,628,621 | Regurgitation , morbidity , and reoperation were similar across treatments , albeit these were associated with very low- quality evidence .
Laparoscopic 270 ° fundoplication achieves a better outcome than 360 ° total fundoplication , especially in terms of postoperative dysphagia , although other types of partial fundoplication might be equally effective . | Despite the extensive literature on laparoscopic antireflux surgery , comparative evidence across different procedures is scarce .
The aim of this study was to assess and rank the most efficacious and safe laparoscopic procedures for the management of gastroesophageal reflux disease . | HYPOTHESIS Laparoscopic anterior 90 degrees partial fundoplication for gastroesophageal reflux is associated with a lower incidence of postoperative dysphagia and other adverse effects compared with laparoscopic Nissen fundoplication . DESIGN A multicenter , prospect i ve , double-blind , r and omized controlled trial . SETTING Nine university teaching hospitals in 6 major cities in Australia and New Zeal and . PARTICIPANTS One hundred twelve patients with proven gastroesophageal reflux disease presenting for laparoscopic fundoplication were r and omized to undergo either a Nissen ( 52 patients ) or an anterior 90 degrees partial procedure ( 60 patients ) . Patients with esophageal motility disorders , patients requiring a concurrent abdominal procedure , and patients who had undergone previous antireflux surgery were excluded from this study . INTERVENTIONS Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication . MAIN OUTCOME MEASURES Independent assessment of dysphagia , heartburn , and overall satisfaction 1 , 3 , and 6 months after surgery using multiple clinical grading systems . Objective measurement of esophageal manometric parameters , esophageal acid exposure , and endoscopic assessment . RESULTS Postoperative dysphagia , and wind-related adverse effects were less common after a laparoscopic anterior 90 degrees partial fundoplication . Relief of heartburn was better following laparoscopic Nissen fundoplication . Overall satisfaction was better after anterior 90 degrees partial fundoplication . Lower esophageal sphincter pressure , acid exposure , and endoscopy findings were similar for both procedures . CONCLUSIONS At the 6-month follow-up , laparoscopic anterior 90 degrees culine partial fundoplication is followed by fewer adverse effects than laparoscopic Nissen fundoplication with full fundal mobilization , and it achieves a higher rate of satisfaction with the overall outcome . However , this is offset to some extent by a greater likelihood of recurrent gastroesophageal reflux symptoms Objective To determine the influence of preoperative esophageal motility on clinical and objective outcome of the Toupet or Nissen fundoplication and to evaluate the success rate of these procedures . Summary background data Nissen fundoplication ( 360 ° ) is the st and ard operation in the surgical management of gastroesophageal reflux disease ( GERD ) . In order to avoid postoperative dysphagia it has been proposed to tailor antireflux surgery according to pre-existing esophageal motility . Postoperative dysphagia is thought to occur more commonly in patients with esophageal dysmotility and it has been recommended to use the Toupet procedure ( 270 ° ) in these patients . We performed a r and omized trial to evaluate this tailored concept and to compare the two operative techniques concerning reflux control and complication rate ( dysphagia ) . Methods 200 patients with GERD were included in a prospect i ve , r and omized study . After preoperative examinations ( clinical interview , endoscopy , 24-hour pH-metry and esophageal manometry ) 100 patients underwent either a laparoscopic Nissen procedure ( 50 with and 50 without motility disorders ) , or Toupet ( 50 with and 50 without motility disorders ) . Postoperative follow-up after two years included clinical interview , endoscopy , 24-hour pH-metry , and esophageal manometry . Results After two years 85 % ( Nissen ) and 85 % ( Toupet ) of patients were satisfied with the operative result . Dysphagia was more frequent following a Nissen fundoplication compared to Toupet ( 19 vs. 8 , p < 0.05 ) and did not correlate with preoperative motility . Concerning reflux control the Toupet proved to be as good as the Nissen procedure . Conclusion Tailoring antireflux surgery according to the esophageal motility is not indicated , as motility disorders are not correlated with postoperative dysphagia . The Toupet procedure is the better operation as it has a lower rate of dysphagia and is as good as the Nissen fundoplication in controlling reflux Background : With the introduction of laparoscopic antireflux surgery ( LARS ) for gastro-oesophageal reflux disease ( GORD ) along with the increasing efficacy of modern medical treatment , a direct comparison is warranted . The 3-year interim results of a r and omised study comparing both the efficacy and safety of LARS and esomeprazole ( ESO ) are reported . Methods : LOTUS is an open , parallel-group multicentre , r and omised and controlled trial conducted in dedicated centres in 11 European countries . LARS was completed according to a st and ardised protocol , comprising a total fundoplication and a crural repair . Medical treatment comprised ESO 20 mg once daily , which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control . The primary outcome variable was time to treatment failure ( Kaplan – Meier analysis ) . Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol . Results : 554 patients were r and omised , of whom 288 were allocated to LARS and 266 to ESO . The two study arms were well matched . The proportions of patients who remained in remission after 3 years were similar for the two therapies : 90 % of surgical patients compared with 93 % medically treated for the intention to treat population , p = 0.25 ( 90 % vs 95 % per protocol ) . No major unexpected postoperative complications were experienced and ESO was well tolerated . However , postfundoplication complaints remain a problem after LARS . Conclusions : Over the first 3 years of this long-term study , both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD INTRODUCTION To evaluate the clinical outcomes of laparoscopic floppy Nissen fundoplication ( LNF ) and laparoscopic Toupet fundoplication ( LTF ) for the treatment of gastroesophageal disease ( GERD ) . METHODS A total of 84 patients with GERD were r and omized to either LNF ( n = 43 ) or LTF ( n = 41 ) between January 2010 and January 2013 . The primary endpoint measures were the DeMeester score , distal esophageal amplitude ( DEA ) , peristaltic frequency , lower esophageal sphincter pressure ( LESP ) , short-term and long-term postoperative dysphagia and recurrence rate . The secondary endpoints were improvements in symptom scores and quality of life ( QoL ) , and perioperative complications . RESULTS LNF group had a lower DeMeester score and a higher LESP compared to LTF group after surgery ( DeMeester score : P = 0.007 ; LESP : P = 0.027 ) . The mean DEA and peristaltic frequency both improved significantly after surgery in 2 groups . There was no difference in the incidence of short-term adverse events ( including dysphagia , heartburn , regurgitation et al. ) between the two groups ( P = 0.157 ) . At the time of the latest follow-up , there was no difference in the incidence of symptomatic reflux symptom ( heartburn and regurgitation ) between the two groups ( heartburn : P = 0.363 ; regurgitation : P = 1.000 ) . A higher frequency of dysphagia was present in the LNF group compared with the LTF group ( P = 0.023 ) . DISCUSSION LNF is associated with an excessive elevation of LESP which may lead to further persistent dysphagia . Partial fundoplication may provide adequate reflux control , improve esophageal body motility and minimize complications associated with an ' over-tight ' fundal wrap . CONCLUSION LTF seems to be as safe and effective on the long-term as LNF , but with a lower incidence of postoperative dysphagia ( ChiCTR-TRC-13003945 ) BACKGROUND Very few r and omized controlled trials ( RCTs ) have compared laparoscopic Nissen fundoplication ( LNF ) to proton pump inhibitors ( PPI ) medical management for patients with chronic gastroesophageal reflux disease ( GERD ) . Larger RCTs have been relatively short in duration , and have reported mixed results regarding symptom control and effect on quality of life ( QOL ) . Economic evaluations have reported conflicting results . OBJECTIVES To determine the incremental cost-utility of LNF versus PPI for treating patients with chronic and controlled GERD over 3 years from the societal perspective . METHODS Economic evaluation was conducted alongside a RCT that enrolled 104 patients from October 2000 to September 2004 . Primary study outcome was GERD symptoms ( secondary outcomes included QOL and cost-utility ) . Re source utilization and QOL data collected at regular follow-up intervals determined incremental cost/QALY gained . Stochastic uncertainty was assessed using bootstrapping and method ologic assumptions were assessed using sensitivity analysis . RESULTS No statistically significant differences in GERD symptom scores , but LNF did result in fewer heartburn days and improved QOL . Costs were higher for LNF patients by $ 3205/patient over 3 years but QOL was also higher as measured by either QOL instrument . Based on total costs , incremental cost-utility of LNF was $ 29,404/QALY gained using the Health Utility Index 3 . Cost-utility results were sensitive to the utility instrument used ( $ 29,404/QALY for Health Utility Index 3 , $ 31,117/QALY for the Short Form 6D , and $ 76,310/QALY for EuroQol 5D ) and if current lower prices for PPIs were used in the analysis . CONCLUSIONS Results varied depending on re source use/costs included in the analysis , the QOL instrument used , and the cost of PPIs ; however , LNF was generally found to be a cost-effective treatment for patients with symptomatic controlled GERD requiring long-term management The aim of the present study was to evaluate the clinical effect of partial and total fundoplication on extraesophageal symptoms in a selected cohort of patients with gastroesophageal reflux disease ( GERD ) . Hundred patients with documented GERD were r and omized to either undergo floppy Nissen ( n=50 ) or Toupet fundoplication ( n=50 ) . Symptom scores of cough , asthma , hoarseness , and distortion of taste were prospect ively evaluated using a st and ardized symptom question naire before surgery and at 3- and 12-month follow-up . Statistical significance was set at a P-value of 0.05 . All evaluated symptoms exhibited substantial improvement after Nissen fundoplication at 3- and 12-month follow-up . Similar therapeutic results were documented for Toupet fundoplication , although statistical significance could not be reached for asthma at long-term follow-up . In conclusion , the application of laparoscopic fundoplication is justified for patients with documented GERD and atypical symptoms refractory to medical treatment . Toupet fundoplication may have a lesser effect on asthma Anterior partial fundoplication ( AF ) has been popularized by a lower risk of mechanical side effects . The question then emerges whether anterior partial wrap has a similar antireflux effect with Nissen fundoplication ( NF ) . We therefore conducted a r and omized study to compare the long-term outcome of anterior fundoplication with NF . One hundred patients who enrolled in the trial from May 2003 to March 2005 were r and omized to laparoscopic AF or laparoscopic NF . Endoscopy , pH monitoring , manometry , a detailed question naire , and a visual analog symptom score were completed preoperative at 6 , 12 , 24 , and 60 months after surgical procedures . The postoperative adverse effects such as dysphagia and flatulence were compared between the two groups . Revision surgery or maintenance proton pump inhibitor therapy was defined as failure . Fifty procedures were performed in each group . The outcome at 5 years follow-up was determined for 96 patients ( 96 % ; 49 patients in the AF group and 47 in the NF group ) . Three patients ( 3 % ) died of unrelated causes during follow-up , and one patient changed address . Both fundoplications were found to provide good control of reflux-related symptoms in most of the patients . For 96 patients followed up more than 5 years , gastroesophageal reflux symptoms were well controlled in 81 patients ( 84.38 % ) ; the mean DeMeester scores in the AF group decreased from 106.89 ± 14.12 to 12.67 ± 3.14 and in the NF group from 109.51 ± 17.98 to 10.81 ± 2.65 , and the esophagitis was ameliorated visibly . Moreover , there were significantly fewer patients in the AF group who complained of flatulence . Compared with NF , anterior 180 ° partial fundoplication is an effective treatment of gastroesophageal reflux and associates with fewer postoperative adverse effects Background The fundoplication of choice for the surgical treatment of gastroesophageal reflux disease ( GERD ) still is debated . Multichannel intraluminal impedance monitoring ( MII ) has not been used to compare objective data , and comparative subjective data on laparoscopic Nissen and Toupet fundoplications are scarce . Methods This study r and omly allocated 125 patients with documented chronic GERD to either laparoscopic floppy Nissen fundoplication ( LNF ; n = 62 ) or laparoscopic Toupet fundoplication ( LTF ; n = 63 ) . The Gastrointestinal Quality of Life Index ( GIQLI ) , symptom grading , esophageal manometry , and MII data were documented preoperatively and 1 year after surgery . The pre- and postprocedure data were compared . Statistical significance was set at a p value lower than 0.01 ( NCT01321294 ) . Results Both procedures result ed in significantly improved GIQLI and GERD symptoms . Preoperative dysphagia improved in both groups , but the improvement reached significance only in the LTF group . The ability to belch was shown to be significantly more decreased after LNF than after LTF . Gas-bloat and “ atypical ” extraesophageal symptoms also were decreased after surgery ( p < 0.01 ) . However , bowel symptoms were virtually unchanged in both groups . Both procedures result ed in significantly improved lower esophageal sphincter pressures . The improvement was greater in the LNF group than in the LTF group ( p < 0.01 ) . The DeMeester score and the numbers of total , acid , proximal , upright , and recumbent reflux episodes decreased in both groups after surgery ( p < 0.01 ) . No significant difference between the procedures in terms of MII data was found . Six patients ( 4.8 % ) had to undergo reoperation because of intrathoracic slipping of the wrap . All the patients had undergone LNF . Conclusions Both procedures proved to be equally effective in improving quality of life and GERD symptoms . However , the reoperation and dysphagia rates were lower and the ability to belch was higher after LTF than after LNF BACKGROUND The effect of total ( Nissen ) and anterior partial fundoplication ( APF ) for the surgical treatment of gastroesophageal reflux disease ( GERD ) on the motor behavior of the esophagogastric axis has not been fully assessed . The purpose of this study was to assess any alterations in lower esophageal sphincter ( LES ) and gastric fundus motor parameters in GERD patients after Nissen or APF fundoplication . METHODS Twenty four patients with documented GERD underwent either laparoscopic Nissen fundoplication ( n = 12 ) or laparoscopic APF ( n = 12 ) . Preoperative and postoperative stationary esophageal manometry included assessment of LES resting and postdeglutition relaxation pressures , intragastric pressure , and LES transient relaxations in the left lateral and upright positions and after gastric distension . RESULTS Both types of fundoplication result ed in significant increases in LES resting ( P < 0.001 ) and postdeglutition relaxation pressure ( P < 0.001 ) in both positions and after gastric distention . Intragastric pressure increased only after Nissen fundoplication in the postgastric distention state ( P = 0.01 ) . Transient LES relaxations were equally abolished after both procedures . All postoperative changes were to a similar level after either procedure with the exception of intragastric pressure after gastric distention , which was significantly higher after total than after partial fundoplication ( P = 0.04 ) . CONCLUSIONS Both procedures equally increase LES resting and postdeglutition relaxation pressures and abolish transient LES relaxations at all states . The significantly higher intragastric pressure at the postgastric distention state after Nissen fundoplication could possibly explain the higher incidence of epigastric fullness and discomfort after this type of antireflux surgery In the operative management of gastro‐oesophageal reflux , a balance must be achieved between adequate control of reflux and excessive dysphagia . The ideal technique is not known . A r and omized study was performed to determine whether laparoscopic anterior fundoplication is associated with a lower incidence of postoperative dysphagia than laparoscopic Nissen fundoplication , while achieving equivalent control of reflux Background The impact of gastroesophageal reflux disease ( GERD ) on the daily lives of patients managed in primary care is not well known . We report the burden of GERD in a large population of patients managed in primary care , in terms of symptoms and impact on patients ' daily lives . Methods RANGE ( R etrospective AN alysis of GE RD ) was an observational study that was conducted at 134 primary care sites across six European countries . All adult subjects who had consulted their primary care physician ( PCP ) during a 4-month identification period were screened retrospectively and those consulting at least once for GERD-related reasons were identified . From this population , a r and om sample of patients was selected to enter the study and attended a follow-up appointment , during which the Reflux Disease Question naire ( RDQ ) , the GERD Impact Scale ( GIS ) and an extra-esophageal symptoms question naire were self-administered . Based on medical records , data were collected on demographics , history of GERD , its diagnostic work-up and therapy . Results Over the 4-month identification period , 373,610 subjects consulted their PCP and 12,815 ( 3.4 % ) did so for GERD-related reasons . From 2678 patients interviewed ( approximately 75 % of whom reported taking medication for GERD symptoms ) , symptom recurrence following a period of remission was the most common reason for consultation ( 35 % ) . At the follow-up visit , with regard to RDQ items ( score range 0–5 , where high score = worse status ) , mean Heartburn dimension scores ranged from 0.8 ( Sweden ) to 1.2 ( UK ) and mean Regurgitation dimension scores ranged from 1.0 ( Norway ) to 1.4 ( Germany ) . Mean overall GIS scores ( range 1–4 , where low score = worse status ) ranged from 3.3 ( Germany ) to 3.5 ( Spain ) . With regard to extra-esophageal symptoms , sleep disturbance was common in all countries in terms of both frequency and intensity . Conclusion In this large European observational study , GERD was associated with a substantial impact on the daily lives of affected individuals managed in the primary care setting Objective The aim of the study was to compare the efficacy and mechanical consequences of 2 partial fundoplications performed laparoscopically under the framework of a r and omized , controlled clinical trial . Summary Background Data Although laparoscopic total fundoplication procedures have proven their effectiveness in the control of gastroesophageal reflux , problems remain with the functional consequences after a supra-competent gastric cardia high-pressure zone . Partial fundoplications have been found to be associated with fewer mechanical side effects . Patients and Methods During a 2-year period , 95 patients with gastroesophageal reflux disease were enrolled into a r and omized , controlled single-institution clinical trial comparing a partial posterior ( Toupét , n = 48 ) fundoplication and an anterior partial wrap ( Watson , n = 47 ) . All patients were assessed postoperatively at predefined time points , and the 12-month follow-up data are presented in terms of clinical results and 24-hour pH monitoring variables . Results Both patient groups were strictly comparable at the time of r and omization . All operations were completed laparoscopically , and no serious complications were encountered . During the first postoperative year , a difference regarding the control of reflux symptoms was observed in favor of the posterior fundoplication . Esophageal acid exposure ( % time pH < 4 ) was substantially reduced by both operations but to a significantly lower level after a Toupét compared with the Watson partial fundoplication ( 1.0 ± 0.3 vs. 5.6 ± 1.1 mean ± SEM ; p < 0.001 ) . Postfundoplication symptoms were infrequently recorded with no difference between the groups . Conclusions When performing a laparoscopic partial fundoplication , the posterior modification ( Toupét ) offers advantages in terms of better reflux control compared with an anterior type ( Watson ) Background A r and omized controlled trial ( RCT ) investigated patients with gastroesophageal reflux disease ( GERD ) who were stable and symptomatically controlled with long-term medical therapy to compare ongoing optimized medical therapy with laparoscopic Nissen fundoplication ( LNF ) . Methods Of the 180 patients eligible for r and omization , 104 gave informed consent , and 3 withdrew from the study immediately after r and omization . The patients r and omized to medical therapy received optimized treatment with proton pump inhibitors ( PPIs ) using a st and ardized management protocol based on best evidence and published guidelines . The surgical patients underwent LNF by one of four surgeons using a previously published technique . The patients underwent symptom evaluation using the GERD symptom scale ( GERSS ) and the global visual analog scale ( VAS ) for overall symptom control . They had 24-h esophageal pH monitoring at baseline and after 3 years . The medical patients were evaluated receiving PPI , and the surgical patients were evaluated not receiving PPI . Results For the 3-year follow-up assessment , 93 patients were available . At 3 years , surgery was associated with more heartburn-free days , showing a mean difference of −1.35 days per week ( p = 0.0077 ) and a lower VAS score ( p = 0.0093 ) than medical management . Surgical patients reported improved quality of life on the general health subscore of the Medical Outcomes Survey Short Form 36 ( SF-36 ) at 3 years , with a mean difference of −12.19 ( p = 0.0124 ) . The groups did not differ significantly in terms of GERSS or acid exposure on 24-h esophageal pH monitoring at 3 years . There were six treatment failures ( 11.8 % ) in the surgical group and eight treatment failures ( 16 % ) in the medical group by 3 years . Conclusions For patients whose GERD symptoms are stable and controlled with PPI , continuing medical therapy and laparoscopic antireflux surgery are equally effective , although surgery may result in better symptom control and quality of life Abstract Background Nissen fundoplication is an effective treatment for gastroesophageal reflux disease ( GERD ) but can cause adverse effects like flatulence and dysphagia . The aim was to compare laparoscopic anterior 120 ° fundoplication ( APF ) to total fundoplication ( Nissen ) concerning flatulence and other adverse effects , in a r and omized blinded study . Methods Seventy-two patients were r and omized to APF ( n = 36 ) or Nissen ( n = 36 ) . Gastroscopy , 24-h pH monitoring and evaluation for symptoms and quality of life using question naires ( GSRS , PGWB and 7- grade d Likert scales ) were performed preoperatively , at 1 and 10 years postoperatively . Patients and the research ers were blinded to operative method . Results When entering the study , most patients had mild – moderate reflux disease according to the symptom score , the 24-h pH measurements , and frequency and grade of esophagitis . At 1-year ( n = 68 ) flatulence , dysphagia , heartburn and acid regurgitation did not differ between groups . More patients could belch ( p = 0.005 ) , and pH monitoring showed a higher time with pH < 4 in the APF group ( p = 0.006 ) . At 10 years ( n = 61 ) , the APF group reported less dysphagia ( p < 0.001 ) , more heartburn ( p = 0.019 ) and more patients could belch ( p = 0.012 ) and vomit ( p < 0.001 ) compared to the Nissen . No difference remained at 10 years in pH monitoring ( n = 23 ) between groups . Symptoms of heartburn and acid regurgitation were less than preoperatively in both groups ( p < 0.001 ) . No revisional operations were performed . Conclusions Both procedures offer good long-term control of reflux symptom , with modest post-fundoplication symptoms . Anterior 120 ° fundoplication results in less dysphagia , better ability to belch and vomit than total fundoplication at 10-year follow-up . The results suggest that APF could be an alternative to Nissen fundoplication in the surgical treatment of mild – moderate GERD This double‐blind , r and omized study compared outcomes of laparoscopic Nissen total fundoplication and anterior partial fundoplication carried out by a single surgeon in a private practice Background A prospect i ve , r and omized trial was performed to evaluate the long-term outcome and patient satisfaction of laparoscopic complete 360 ° fundoplication compared with partial posterior 270 ° fundoplication . Partial fundoplication is purported to have fewer side effects with a higher failure rate in controlling gastroesophageal reflux disease ( GERD ) , while complete fundoplication is thought to result in more dysphagia and gas-related symptoms . Methods Patients were r and omized to either laparoscopic Nissen ( LN ) or laparoscopic Toupet ( LT ) fundoplication . Esophageal manometry , 24-h pH studies , a detailed question naire , and a visual analog symptom ( VAS ) score were completed before and after surgery . A final global outcome question naire was performed . Failure was defined as recurrent GERD requiring revision surgery , maintenance proton pump inhibitor ( PPI ) therapy , or surgery for postoperative dysphagia . Results One hundred patients were r and omized to LN ( 50 ) or LT ( 50 ) . There were no differences between LN and LT with respect to postoperative symptoms and physiological variables except a higher wrap pressure in the LN group ( 15.2 vs. 12.0 mmHg ) . Dysmotility improved in 8/14 ( 57 % ) and 6/11 ( 54 % ) patients in the LN group and the LT group , respectively , after surgery . There was no correlation between dysmotility and dysphagia both pre- and post surgery in the two groups . Recurrent symptoms of GERD occurred in 8/47 ( 17.0 % ) and 8/48 ( 16.6 % ) in the LN group and the LT group , respectively . Outcome of patients with dysmotility was similar to those with normal motility in both groups . At final follow-up ( 59.76 ± 24.23 months ) , in the LN group , 33/37 ( 89.1 % ) would recommend surgery to others , 32/37 ( 86.4 % ) would have repeat surgery , and 34/37 ( 91.8 % ) felt they were better off than before surgery . The corresponding numbers for the LT group ( follow-up = 55.18 ± 25.97 months ) were 35/36 ( 97.2 % ) , 30/36 ( 83.3 % ) , and 33/36 ( 91.6 % ) . Conclusion LN and LT are equally effective in restoring the lower esophageal sphincter function and provide similar long-term control of GERD with no difference in dysphagia . Esophageal dysmotility had no influence on the outcome of either operation Background Incontinence or hypercontinence of the fundic wrap depends primarily on the length of the valve or the type of procedure . Much less attention has been paid to the fundic wrap length . This study aim ed to compare the effectiveness of two different wrap lengths among the patients undergoing partial or total fundoplication . Methods For this study , 153 patients were r and omized to either Nissen ( 1.5- or 3-cm wrap ) or Toupet ( 1.5- or 3-cm wrap ) laparoscopic fundoplication . The groups were compared according to intensity of dysphagia , esophageal manometry data , ambulatory 24-h pH monitoring data , postoperative esophagitis rate , and overall treatment failure rate . Results In all the groups , the tone of the lower esophageal sphincter was significantly increased and the DeMeester score significantly decreased , reaching normal levels . At 6 months after surgery , the Toupet 1.5-cm group had significantly more cases of esophagitis than the 3-cm wrap group ( 24.2 % vs 3.3 % ; p < 0.05 ) . At 12 months after surgery , only one patient in the Nissen 3-cm group had moderate to severe dysphagia . In all cases , failures were associated with persistent erosive esophagitis . At the 12-month follow-up assessment , treatment failures were significantly more common in Toupet 1.5-cm group than in the Toupet 3-cm group ( 17.5 % vs 2.7 % ; p < 0.05 ) . However , such differences were not observed in the Nissen groups ( 7.8 % for 1.5 cm and 15.6 % for 3 cm ; p > 0.05 ) . Conclusions Evaluation of the treatment results suggests that the wrap length is important in partial Toupet fundoplication to avoid treatment failures . The 3-cm wrap is superior to the 1.5-cm wrap in cases of partial posterior Toupet fundoplication . The influence of wrap length on treatment failure remains unconfirmed for the Nissen procedure Background Laparoscopic Toupet fundoplication ( TF ) is reported to be as effective as Nissen ( NF ) , but to be associated with fewer unfavorable postoperative side-effects . This study evaluates the one- and three-year clinical outcome of 140 r and omized patients after a laparoscopic NF or TF . Patients and methods Inclusion criteria included patients over 16 years old with complications of gastro-oesophageal reflux disease ( GORD ) and persistence or recurrence of symptoms after three months of treatment . Subjects with a previous history of gastric surgery or repeated fundoplication , brachy-oesophagus or severe abnormal manometry results were excluded . Seventy-seven NF and 63 TF were performed . The severity of symptoms was assessed before and after the procedure . Results One hundred and twenty-one of the 140 patients after one year , and 118 after three years , were evaluated and no statistically significant clinical difference was observed . The level of satisfaction concerning the outcome of the operation remained high after one or three years regardless of the type of fundoplication performed . Conclusions Functional complications after NF are not avoided with TF Laparoscopic Nissen fundoplication and proton pump inhibitor ( PPI ) therapy are both established treatments for gastroesophageal reflux disease ( GERD ) . We have performed a prospect i ve r and omized study comparing these two treatments and now have long-term follow-up data . Between July 1997 and August 2001 , 183 patients in Norwich took part in a r and omized controlled trial comparing laparoscopic Nissen fundoplication and PPI therapy for the treatment of GERD . In October 2005 , patients were followed up and asked to complete a reflux symptom question naire . Ninety-one patients were r and omized to have surgery and 92 to have optimized PPI therapy . After 12 months , those who had been r and omized to PPI were offered the opportunity to have surgery . Fifty-four patients went on to have antireflux surgery ; the remaining 38 did not . In all three groups , there was a significant improvement in symptom score after the initial 12 months ( P<0.01 ; Mann-Whitney U test ) . However , those who later had surgery despite having had optimal PPI treatment beforeh and experienced further symptomatic improvement ( P<0.01 ) at long-term follow-up ( median 6.9 years , range , 4.3–8.3 ) . Both optimal PPI therapy and laparoscopic Nissen fundoplication are effective treatments for GERD . However , surgery offers additional benefit for those who have only partial symptomatic relief whilst on PPIs Background Although symptom outcomes following laparoscopic fundoplication have been adequately evaluated in the past , comparative subjective data of laparoscopic Nissen and Toupet fundoplications are scarce . Multichannel intraluminal impedance monitoring ( MII ) has not been used so far for comparison of objective data . Methods One hundred patients with documented chronic gastroesophageal reflux disease ( GERD ) were r and omly allocated to either floppy Nissen fundoplication ( group I , n = 50 ) or Toupet fundoplication ( group II , n = 50 ) . Gastrointestinal Quality of Life Index ( GIQLI ) , symptom grading , esophageal manometry , and MII data were documented preoperatively and 3 months after surgery . Subjective and objective outcome data were compared to those of healthy individuals . Results Symptom intensity was significantly more severe and GIQLI showed impairment in the examined patient population compared to healthy controls . Both procedures result ed in a significant improvement in GIQLI and GERD symptoms ( p < 0.01 ) . Dysphagia improved significantly only in group II , while cough , asthma , and distortion of taste improved significantly in both groups . Hoarseness symptoms showed some degree of improvement in both groups but reached statistical significance only in group I. Postoperatively , bowel symptoms partly increased and the ability to belch decreased in both groups ( p < 0.05 ) . Comparison of postoperative GIQLI and symptom scores showed no significant difference between the two groups , except for the ability to belch , which was more impaired after Nissen fundoplication . Both procedures result ed in a significant improvement in lower esophageal sphincter ( LES ) pressure ; however , the improvement was greater in group I than in group II . MII data showed more reflux control after Nissen , but the differences between the procedures were not significant . Conclusions Both procedures equally improve quality of life and GERD symptoms . Bowel symptoms may increase after both procedures at the 3-month follow-up . Manometry and MII data favor Nissen fundoplication , but dysphagia and the inability to belch are more common compared to Toupet fundoplication BACKGROUND It has been proposed that partial fundoplication is associated with less incidence of postoperative dysphagia and consequently is more suitable for patients with gastroesophageal reflux disease ( GERD ) and impaired esophageal body motility . The aim of this study was to assess whether outcomes of Toupet fundoplication ( TF ) are better than those of Nissen-Rossetti fundoplication ( NF ) in patients with GERD and low-amplitude esophageal peristalsis . STUDY DESIGN Thirty-three consecutive patients with proved GERD and amplitude of peristalsis at 5 cm proximal to lower esophageal sphincter ( LES ) less than 30 mmHg were r and omly allocated to undergo either TF ( 19 patients : 11 men , 8 women ; mean age : 61.7 + /- 8.7 SD years ) or NF ( 14 patients : 7 men , 7 women ; mean age : 59.2 + /- 11.5 years ) , both by the laparoscopic approach . Pre- and postoperative assessment included clinical question naires , esophageal radiology , esophageal transit time study , endoscopy , stationary manometry , and 24-hour ambulatory esophageal pH testing . RESULTS Duration of operation was significantly prolonged in the TF arm ( TF : 90 + /- 12 minutes versus NF : 67 + /- 15 minutes ; p < 0.001 ) . At 3 months postoperatively , the incidences of dysphagia ( grade s I , II , III ) and gas-bloat syndrome were higher after NF than after TF ( NF : 57 % versus TF : 16 % ; p < 0.01 and NF : 50 % versus TF : 21 % ; p = 0.02 , respectively ) , but decreased to the same level in both groups at the 1-year followup ( NF : 14 % versus TF : 16 % and NF : 21 % versus TF : 16 % , respectively ) . At 3 months postoperatively , patients with NF presented with significantly increased LES pressure than those with TF ( p = 0.02 ) , although LES pressure significantly increased after surgery in both groups , as compared with preoperative values . Amplitude of esophageal peristalsis at 5 cm proximal to LES increased postoperatively to the same extent in both groups ( TF , preoperatively : 21 + /- 6 mmHg versus postoperatively : 39 + /- 12 mmHg ; p < 0.001 , and NF , preoperatively : 20 + /- 8 mmHg versus postoperatively : 38 + /- 12 mmHg ; p < 0.001 ) . Reflux was abolished in all patients of both groups . CONCLUSIONS Both TF and NF efficiently control reflux in patients with GERD and low amplitude of esophageal peristalsis . Early in the postoperative period , TF is associated with fewer functional symptoms , although at 1 year after surgery those symptoms are reported at similar frequencies after either procedure Objective : To investigate late objective outcomes 14 years after laparoscopic anterior 180-degree partial versus Nissen fundoplication . Background : Clinical outcomes from r and omized clinical trials suggest good outcomes for anterior 180-degree partial fundoplication , with similar control of reflux symptoms and less side effects , compared with Nissen fundoplication . However , objective outcomes at late follow-up have not been reported . Methods : A subset of participants from a r and omized trial of anterior 180-degree versus Nissen fundoplication underwent stationary esophageal high-resolution manometry and ambulatory 24-hour impedance-pH monitoring at 14 years ' follow-up . The subset and other patients in the trial also completed a st and ardized clinical question naire to ensure that they were representative of the overall trial . Results : Eighteen patients ( 8 anterior , 10 Nissen ) underwent objective testing and had a symptom profile similar to those who did not ( n = 59 ) have testing . Total esophageal acid exposure time and the total number of acid and weakly acidic reflux episodes per 24 hours were higher after anterior fundoplication than after Nissen fundoplication . Proximal , midesophageal and distal reflux were proportionately increased after anterior 180-degree fundoplication . The number of liquid and mixed reflux episodes was also higher after anterior fundoplication , which was accompanied by higher clinical heartburn scores . There were no differences in gas reflux , gastric belches , and supragastric belches , which is in line with the observation that gas-related symptoms were similar for both groups . Mean LES resting and relaxation nadir pressure were lower after anterior fundoplication , which was reflected by lower dysphagia scores . Patient satisfaction was similar after both procedures . Conclusions : At 14 years after r and omization , this study demonstrated that acid , weakly acidic , liquid and mixed reflux episodes are more common after anterior 180-degree fundoplication than after Nissen fundoplication . On the contrary , gas reflux and gastric belching and patient satisfaction are similar for both procedures . Mean LES resting and relaxation nadir pressure are lower after anterior fundoplication . Overall , these findings suggest less effective reflux control after anterior 180-degree partial fundoplication , offset by less dysphagia , leading to a clinical outcome that is equivalent to Nissen fundoplication at late follow-up Background Long-term results in antireflux surgery may depend on fundoplication type and wrap length . We compared the outcome of two different wrap lengths among the patients undergoing partial or total fundoplications . This study is the next part of a prospect i ve 5-year follow-up assessment . Methods A total of 153 patients were r and omized to Nissen or Toupet 1.5- or 3-cm wrap laparoscopic fundoplication . The primary endpoint — treatment failure rate was defined as a recurrent GERD or persistent dysphagia . Intensity of heartburn , dysphagia , gas-bloating , presence of esophagitis were assessed as a secondary outcome at 1-year and 5-year follow-up . Results At 5-year follow-up , data were collected from 129 ( 85 % ) patients . At 1-year follow-up , 17 ( 11 % ) treatment failures were detected . At the end of the fifth year , the numbers reached 23 ( 15 % ) . The failures were more common in the 1.5-cm Toupet ( 25 % ) and the 3-cm Nissen group ( 18.2 % ) . The significant difference in failure rates was found between 1.5-cm and 3-cm Toupet groups ( P < 0.05 ) . Dysphagia remained low during the follow-up in all of the groups . The prevalence of higher scores of heartburn after 5 years was detected in Nissen 1.5-cm group ( 20.8 % ) . The lowest scores were observed in Toupet 3-cm group . Bloating symptoms were more prevalent among Nissen and Toupet 3-cm group patients at 5-year follow-up . At the end of the fifth year , the prevalence of esophagitis was lower in Nissen 1.5-cm ( 19.3 % ) and Toupet 3-cm ( 13.3 % ) groups . The highest prevalence of esophagitis—32.4 % —was found in Toupet 1.5-cm group . Conclusions Nissen and Toupet fundoplication achieved sufficient control of reflux with success rate of 85 % at 5-year follow-up . There were no significant differences in the postoperative dysphagia , esophagitis , and bloating rates . However , the distribution of treatment failures leads us to conclude that 1.5-cm wrap length is insufficient in cases of posterior partial fundoplication Introduction : Fundoplication techniques for treatment of gastroesophageal reflux are discussed concerning impairments and success . This r and omized trial was conducted to compare Nissen ’s wrap and the anterior partial technique ( Dor ) concerning patients ’ quality of life ( QoL ) and functional data after a mid-term follow-up . Methods : In a 24-month period , 64 patients were equally r and omized into group A ( Nissen ’s fundoplication ) and group B ( 180 ° anterior partial fundoplication ) . After a mean follow-up of 18 months , all patients were examined and interviewed using st and ardized QoL question naires ( Gastrointestinal Quality of Life Index ) , Visick score , 24-hour pH-metry and esophageal manometry . Data of 57 patients ( group A : 27 , group B : 30 ) could be analyzed . Results : After partial fundoplication , 9 patients ( 30 % ) stated the operative results were worse than perfect . Only 2 patients ( 7 % ) evaluated the outcome after Nissen ’s fundoplication as unsuccessful ( p = 0.04 ) . However , postoperative Gastrointestinal Quality of Life Index showed no differences between groups ( p = 0.5 ) . Additionally , functional data were not different ( DeMeester 10 vs. 12 , p = 0.17 , and lower esophageal sphincter pressure 13 vs. 12 mm Hg , p = 0.5 ) . Conclusion : The anterior partial fundoplication technique did not lead to disadvantages in postoperative QoL , physiological function and reflux control when compared to Nissen ’s approach in a mid-term follow-up HYPOTHESIS Laparoscopic 90 degrees anterior partial fundoplication for gastroesophageal reflux disease achieves equivalent results to laparoscopic Nissen fundoplication . DESIGN A multicenter , prospect i ve , double-blind r and omized clinical trial with a minimum of 5 years ' follow-up . SETTING Nine university teaching hospitals in 6 major cities throughout Australia and New Zeal and . PARTICIPANTS One hundred twelve patients undergoing primary antireflux surgery were r and omized to undergo either laparoscopic Nissen fundoplication ( 52 patients ) or anterior 90 degrees partial fundoplication ( 60 patients ) . INTERVENTIONS Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication . MAIN OUTCOME MEASURES Blinded assessment at 1 and 5 years ' follow-up of clinical outcome for postoperative heartburn , dysphagia , gas-related symptoms , and satisfaction with the surgical outcome . Analog scales ranging from 0 to 10 were used to assess symptom severity . RESULTS Ninety-seven patients underwent follow-up at 5 years . Three others died during follow-up , 4 refused follow-up , and 8 were lost to follow-up ; 89 % remained at 5-years ' follow-up . At 5 years ' follow-up , mean analog scores for heartburn were 2.2 for anterior fundoplication vs 0.9 for Nissen fundoplication ( P=.003 ) . There were no significant differences between the groups for dysphagia scores . The mean score for outcome satisfaction was 7.1 after anterior fundoplication vs 8.1 after Nissen fundoplication ( P=.18 ) . Eighty-eight percent reported a good or excellent outcome following Nissen fundoplication vs 77 % following anterior fundoplication . CONCLUSIONS Laparoscopic Nissen and anterior 90 degrees partial fundoplication achieve similar levels of patient satisfaction at 5 years ' follow-up , with similar adverse effect profiles . However , at 5 years ' follow-up , laparoscopic Nissen fundoplication achieves superior control of reflux symptoms . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Register Identifier : ACTRN12607000298415 Background Partial fundoplications have been popularized by their lower risk of mechanical side effects . The question then emerges whether a similar partial wrap should be done posterior or anterior to the distal esophagus ? We therefore conducted a study to compare the long-term outcome of laparoscopic partial fundoplications constructed either as anterior ( AF ) or posterior ( PF ) repairs . Patients and Methods Ninety-five patients were enrolled in a r and omized clinical trial . After a mean follow up of 65 months , 43 AF and 45 PF patients remained in the study . The levels of reflux control and postfundoplication complaints were assessed by use of vali date d instruments . Results A posterior fundoplication was found to provide significantly better control of reflux related symptoms ( heartburn p < 0.0001 , acid regurgitation p < 0.0001 ) . This was also reflected in a significantly lower number of reoperations and need for antisecretory drug therapy . The earlier postoperative difference in postfundoplication symptoms had disappeared . Conclusions A laparoscopic posterior partial fundoplication offers a high and durable level of disease control with few side effects . The current anterior type of repair can not be recommended due to insufficient reflux control Background Nissen fundoplication ( 360 ° ) is the st and ard operation for the surgical management of gastroesophageal reflux disease ( GERD ) . To avoid postoperative dysphagia , it has been proposed that antireflux surgery be tailored according to the degree of preexisting esophageal motility . Postoperative dysphagia is thought to occur more commonly in patients with esophageal dysmotility and the Toupet procedure ( 270 ° ) has been recommended for these patients . We performed a r and omized trial to evaluate this tailored concept and to compare the two operative techniques in terms of reflux control and complication rate ( dysphagia ) . Our objective was to determine the impact of preoperative esophageal motility on the clinical and objective outcome , following Toupet vs Nissen fundoplication and to evaluate the success rate of these procedures . Methods From May 1999 until May 2000 , 200 patients with GERD were included in a prospect i ve r and omized study . After preoperative examinations ( clinical interview , endoscopy , 24-h pH study and esophageal manometry ) , 100 patients underwent either a laparoscopic Nissen ( 50 with and 50 without motility disorders ) , or a Toupet procedure ( 50 with and 50 without motility disorders ) . Postoperative follow-up after 4 months included clinical interview , endoscopy , 24-h pH study and esophageal manometry . Results Interviews showed that 88 % ( Nissen ) and 90 % ( Toupet ) of the patients , respectively , were satisfied with the operative result . Dysphagia was more frequent following a Nissen fundoplication than after a Toupet ( 30 vs 11 , p<0.001 ) and did not correlate with preoperative motility . In terms of reflux control , the Toupet proved to be as effective as the Nissen procedure . Conclusion Tailoring antireflux surgery to esophageal motility is not indicated , since motility disorders are not correlated with postoperative dysphagia . The Toupet procedure is the better operation because it has a lower rate of dysphagia and is as effective as the Nissen fundoplication in controlling reflux This study examined the short‐term cost‐effectiveness and long‐term cost of laparoscopic Nissen fundoplication ( LNF ) versus maintenance proton‐pump inhibitor ( PPI ) medication for severe gastro‐oesophageal reflux disease ( GORD ) based on a r and omized clinical trial A r and omized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor ( n = 52 ) with laparoscopic Nissen fundoplication ( n = 52 ) . Patients were monitored for 1 year . The primary end point was frequency of gastroesophageal reflux dis-ease symptoms . Surgical patients had improved symptoms , pH control , and overall quality of life health index after surgery at 1 year compared with the medical group . The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients , but improved in the surgical patients . Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose , but 6 had satisfactory symptom remission . No surgical patients required additional treatment for symptom control . Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical c and i date s and should experience improved symptom control after surgery at 1 year OBJECTIVE A prospect i ve , r and omized trial was performed to determine which of two antireflux procedures , a complete wrap ( Nissen ) or a 200N wrap ( Toupet ) , was more effective with fewer sequelae . SUMMARY BACKGROUND DATA Laparoscopic procedures for gastroesophageal reflux disease appear to be as effective as those done by open laparotomy . The Nissen fundoplication is used most frequently , but postoperative bloating , inability to belch , and dysphagia occur . The partial wrap has been said to be as effective with less unfavorable postoperative symptoms . METHODS Patients with reflux esophagitis were approached laparoscopically using a six-port technique . After division of the short gastric vessels and dissection of the terminal esophagus and fundus of the stomach to allow performance of either procedure , patients r and omly were assigned one of the procedures by a card drawn in the operating room . RESULTS Forty patients underwent operation , but 1 was excluded when an open procedure became necessary . Twenty-three patients received a complete wrap and 16 received a partial wrap . The average operating time was 155 minutes for the Nissen procedures and 162 minutes for the Toupet procedures . The postoperative stay averaged 2.7 days for the Nissen procedures and 2.5 days for the Toupet procedures . There were no deaths . Including the patient converted to an open procedure , three patients had operative complications . At follow-up , Visick scores after the complete wraps were I-13 , II-8 , III-2 and after the partial wrap were I-12 and II-3 . Two patients indicated they would not have the operation again . CONCLUSIONS A partial or a complete wrap after division of the short gastric vessel offers effective therapy for reflux esophagitis with > 90 % patient satisfaction . The authors ' study shows no clear advantage of one wrap ( partial or complete ) over the other AIM To compare the advantages and disadvantages of laparoscopic Nissen and Toupet fundoplication in the treatment of gastroesophageal reflux disease ( GERD ) and their indications . PATIENTS AND METHODS From June 2001 to December 2011 , 383 patients with GERD were r and omized into two groups according to the last number in their hospitalization number . Overall , 215 patients underwent laparoscopic Nissen fundoplication , and 168 underwent laparoscopic Toupet fundoplication . RESULTS No conversions to laparotomy or deaths were observed , and the symptoms disappeared completely postoperatively in both groups . Average follow-up was 5.6 years . No recurrence of symptoms was observed in the Nissen group . Eighteen patients experienced recurrence of symptoms in the Toupet group and were administered acid-suppressing drugs . Esophageal manometry and acid reflux testing were performed 4 months postoperatively , with normal results in both groups . The cure rate of esophageal inflammation was 88.4 % in the Nissen group and 67.7 % in the Toupet group . Four days postoperatively , the incidences of dysphagia and abdominal distension were significantly higher in the Nissen group compared with the Toupet group ( 28.4 % and 16.7 % , respectively ) ; the difference between the two groups significantly decreased 1 year postoperatively ( 1.5 % and 0.8 % , respectively ) . CONCLUSIONS In the short term , the incidence of dysphagia was significantly lower after Toupet fundoplication , but the difference decreased significantly with extension of the postoperative recovery period . For patients with moderate to severe GERD , the laparoscopic Nissen fundoplication may be optimal ; for elderly patients or for patients with significantly reduced esophageal peristalsis detected in preoperative examinations , the laparoscopic Toupet fundoplication should be considered Objective . To compare the effect of laparoscopic Nissen and Lind fundoplication on gastro-oesophageal reflux disease by means of a prospect i ve r and omized controlled trial . Material and methods . One hundred and twenty-one patients were r and omized to undergo either Nissen ( 61 ) or Lind ( 60 ) fundoplication . Initial enrolment and subsequent clinical appointments were undertaken 1 , 3 , 6 and 12 months after the procedure using a st and ardized question naire . Ambulatory pH monitoring and manometry were undertaken both preoperatively and at approximately 3 months post-procedure . Results . The mean operating time was similar in both groups ( 44.8 versus 45 min ) . One operation in the Lind group was converted to open surgery . Postoperative dysphagia symptoms at 3 and 6 months were higher in the Nissen fundoplication group than in the Lind group ( 3 months p=0.003 ; 6 months p=0.020 ) . The time taken to return to work was statistically longer in the Nissen group : at 1 month , 9 of 40 versus 2 of 45 patients had not returned to full activities ( p=0.013 ) . Three individuals required re-operation in the Nissen group and 4 individuals in the Lind group because of dysphagia caused by mechanical obstruction . Both procedures demonstrated good Visick scores at 12 months ; the Nissen group having 33 ( 97 % ) patients with a Visick score of 1 or 2 , and the Lind group having 38 ( 100 % ) patients with a Visick score of 1 or 2 . Conclusions . Both operations provide good quantitative and qualitative control of gastro-oesophageal reflux . Operation time and postoperative comparators were similar in both groups . There were no statistically significant differences between the groups at 1 year A r and omized trial of laparoscopic Nissen fundoplication and anterior 180 ° partial fundoplication was undertaken to determine whether the anterior procedure might reduce the incidence of dysphagia and other adverse outcomes following surgery for gastro‐oesophageal reflux disease . This study evaluated clinical outcomes after 10 years BACKGROUND Laparoscopic Hill repair ( LHR ) and laparoscopic Nissen fundoplication ( LNF ) are established surgical antireflux procedures but have never been compared in a prospect i ve trial . This trial was design ed to compare the effectiveness of LHR against the gold-st and ard LNF . METHODS Patients with uncomplicated gastroesophageal reflux from two esophageal centers were r and omly assigned and blinded from 2003 to 2007 . Preoperative and postoperative evaluation included two quality of life metrics-- Quality of Life in Reflux and Dyspepsia , and Dysphagia -- as well as endoscopy , video esophogram , manometry , and pH testing . RESULTS Of 121 patients who consented to the trial , 102 underwent surgery ; 46 LNF and 56 LHR were performed , with a mean follow-up of 12 months . Postoperatively , the DeMeester score normalized for both repairs , with no difference between them ( LNF 6.8 , LHR 11.1 , p=0.26 ) . Postoperative medication use was 4 % , and the groups were equivalent . Lower esophageal sphincter pressure increased significantly for LNF ( 14.93 to 24.10 , p=0.001 ) but not for LHR ( 19.91 to 20.25 , p=0.87 ) . Quality of life scores improved significantly for both repairs ( LNF 3.77 to 6.65 ; LHR 3.84 to 6.54 , p<0.001 ) , and postoperative results were equivalent ( p=0.99 ) . Dysphagia scores preoperative/postoperative were LNF 33.88 to 38.33 and LHR 35.44 to 38.72 , and were equivalent postoperatively ( p=0.94 ) . Two LNF and two LHR required reoperation for failed repair . CONCLUSIONS The LHR and the LNF both yield excellent and equivalent results for uncomplicated gastroesophageal reflux at 12 months . Their mechanisms of action may be different Both laparoscopic Nissen fundoplication ( LNF ) and proton‐pump inhibitor ( PPI ) therapy are established in the treatment of gastro‐oesophageal reflux disease ( GORD ) . The aim of this study was to compare these two treatments in a r and omized clinical trial Introduction Nissen fundoplication can be followed by side effects , and this has driven modifications , including partial fundoplications . We previously reported early outcomes from a r and omised trial of Nissen vs anterior 90 ° partial fundoplication . This paper reports 5-year follow-up outcomes to determine whether anterior 90 ° fundoplication achieves a satisfactory longer-term outcome . Methods From February 1999 to August 2003 , 79 patients were r and omised to Nissen vs anterior 90 ° fundoplication . Patients were followed yearly using a st and ardized clinical question naire which included symptom scores to assess heartburn , dysphagia , other post-fundoplication side effects and overall satisfaction with the outcome . Five-year clinical outcomes were analysed . Results Seventy-four patients were available for follow-up at 5 years . There were no significant differences for heartburn or satisfaction , although more patients used antisecretory medication after anterior 90 ° fundoplication ( 29.7 vs 8.1 % ) . Dysphagia was greater after Nissen fundoplication when measured by an analogue score for solid food and a composite dysphagia score . Symptoms of bloating were more common following Nissen fundoplication ( 80.0 vs 32.4 % ) , and less patients could eat a normal diet ( 78.4 vs 94.6 % ) . Re-operation was undertaken in four patients after Nissen fundoplication ( dysphagia , three ; hiatus hernia , one ) vs three after anterior 90 ° fundoplication ( recurrent reflux , three ) . Conclusions At 5 years , anterior 90 ° partial fundoplication was associated with less side effects , offset by greater use of antisecretory medication . Reflux symptoms and overall satisfaction were similar to Nissen fundoplication . Laparoscopic anterior 90 ° partial fundoplication is an effective treatment for gastro-esophageal reflux Background : The aim of the study was to compare the effect of laparoscopic anterior and posterior fundoplication on gastro‐oesophageal reflux disease by means of a prospect i ve r and omized controlled trial |
442 | 21,824,386 | Conclusions A small majority ( just over half ) of CCDSSs improved care processes in chronic disease management and some improved patient health . | Background The use of computerized clinical decision support systems ( CCDSSs ) may improve chronic disease management , which requires recurrent visits to multiple health professionals , ongoing disease and treatment monitoring , and patient behavior modification .
The objective of this review was to determine if CCDSSs improve the processes of chronic care ( such as diagnosis , treatment , and monitoring of disease ) and associated patient outcomes ( such as effects on biomarkers and clinical exacerbations ) . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions We developed a computer-stored medical record system containing a limited set of the total clinical data base -- primarily diagnostic studies and treatments . This system responds to its own content according to physician-authored reminder rules . To determine the effect of the reminder messages generated by 1490 rules on physician behavior , we r and omly assigned practitioners in a general medicine clinic to study or control groups . The computer found indications for six different actions per patient in 12 467 patients during a 2-year study : 61 study group residents who received computer reminders responded to 49 % of these indications ; 54 control group residents , to only 29 % ( p less than 0.0001 ) . Preventive care ( occult blood testing , mammographic screening , weight reduction diets , influenza and pneumococcal vaccines ) was affected . The intentions of the study group to use a given action for an indication predicted their response to the indications ( p less than 0.03 , r2 = 0.33 ) . The intentions of the control residents did not OBJECTIVE To assess the impact and cost-effectiveness of two information-based provider reminder interventions design ed to improve self-care management and outcomes of heart failure ( HF ) patients . DATA SOURCES / STUDY SETTING Interview and agency administrative data on 628 home care patients with a primary diagnosis of HF . STUDY DESIGN Patients were treated by nurses r and omly assigned to usual care or one of two intervention groups . The basic intervention was an e-mail to the patient 's nurse highlighting six HF-specific clinical recommendations . The augmented intervention supplemented the initial nurse reminder with additional clinician and patient re sources . DATA COLLECTION Patient interviews were conducted 45 days post admission to measure self-management behaviors , HF-specific outcomes ( Kansas City Cardiomyopathy Question naire-KCCQ ) , health-related quality of life ( EuroQoL ) , and service use . PRINCIPAL FINDINGS Both interventions improved the mean KCCQ summary score ( 15.3 and 12.9 percent , respectively ) relative to usual care ( p < or = .05 ) . The basic intervention also yielded a higher EuroQoL score relative to usual care ( p < or = .05 ) . In addition , the interventions had a positive impact on medication knowledge , diet , and weight monitoring . The basic intervention was more cost-effective than the augmented intervention in improving clinical outcomes . CONCLUSIONS This study demonstrates the positive impact of targeting evidence -based computer reminders to home health nurses to improve patient self-care behaviors , knowledge , and clinical outcomes . It also advances the field 's limited underst and ing of the cost-effectiveness of selected strategies for translating research into practice OBJECTIVE —The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practice s. RESEARCH DESIGN AND METHODS —This was a group-r and omized , controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention ( TRANSLATE ) in 24 practice s. The intervention included implementation of an electronic diabetes registry , visit reminders , and patient-specific physician alerts . A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion . The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure ( SBP ) < 130 mmHg , LDL cholesterol < 100 mg/dl , and A1C < 7.0 % at baseline and 12 months . Six process measures were also followed . RESULTS —Over 24 months , 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practice s from 17 health systems . Diabetes process measures increased significantly more in intervention than in control practice s , giving net increases as follows : foot examinations 35.0 % ( P < 0.0.001 ) ; annual eye examinations 25.9 % ( P < 0.001 ) ; renal testing 28.5 % ( P < 0.001 ) ; A1C testing 8.1%(P < 0.001 ) ; blood pressure monitoring 3.5 % ( P = 0.05 ) ; and LDL testing 8.6 % ( P < 0.001 ) . Mean A1C adjusted for age , sex , and comorbidity decreased significantly in intervention practice s ( P < 0.02 ) . At 12 months , intervention practice s had significantly greater improvement in achieving recommended clinical values for SBP , A1C , and LDL than control clinics ( P = 0.002 ) . CONCLUSIONS — Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes BACKGROUND Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits . METHODS We conducted a r and omized controlled trial of a 12-month intervention at 2 large community health centers , enrolling 310 patients with a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of 25 or greater . In the intervention group , self-management goals for nutrition and physical activity were set using a tailored computer program . Goals were then review ed at each clinic visit by physicians . The control group received only printed health education material s. The main outcome measures included change in physical activity and body weight . RESULTS In the intervention group , recommended levels of physical activity increased from 26 % at baseline to 53 % at 12 months ( P < .001 ) compared with controls ( 30 % to 37 % ; P= .27 ) , and 32 % of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9 % of controls ( odds ratio , 2.2 ; P= .006 ) . CONCLUSION A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss The purpose of the study was to compare the proportion of obesity-related diagnoses in clinical encounters ( N = 1874 ) documented by nurses using a personal digital assistant-based log with and without obesity decision support features . The experimental group encounters in the r and omized controlled trial had significantly more ( P = .000 ) obesity-related diagnoses ( 11.3 % ) than did the control group encounters ( 1 % ) and a significantly lower false negative rate ( 24.5 % vs 66.5 % , P = .000 ) . The study findings provide evidence that integration of a decision support feature that automatically calculates an obesity-related diagnosis increases diagnoses and decreases missed diagnoses and suggest that such systems have the potential to improve the quality of obesity-related care Purpose : Physicians and patients frequently miss opportunities to improve the quality of care of diabetes , primarily because of the complexity of managing many risk factors over many years with many other providers . Electronic decision support is a potential way to improve prescribing and quality of care . Shared care , meaning patients and physicians sharing access to the patient ’s status compared to recommended targets , is thought to improve outcomes as are supportive reminders . Our objective was to rigorously evaluate whether an electronic medical record (EMR)-linked , individualized electronic diabetes tracker with automated telephone reminders could improve the quality of diabetes management in primary care . Methods : Community-based family physicians across Ontario who were already using EMRs in their practice , were recruited . Patient and physician versions of a Web-based diabetes tracker , the ( COMPETE II Diabetes Tracker ( CIIDT ) system , were developed . The main tracker page showed all 13 monitoring variables – the patient ’s recent values , both process ( when last checked ) and outcome ( the result ) , target values for process and outcome , and short advisory messages , with red/yellow/green highlighting to indicate urgency of review . Links to best evidence guidelines and patient re sources were provided . The physician view appeared as an overlay in a corner of their own electronic medical record ( N = 6 EMR products ) . Intervention patients were linked to a voice biometric-enabled automated telephone reminder system ( ATRS ) for medications , labs and visits . Consenting patients with diabetes were r and omized to the CIIDT-ATRS intervention or usual care ( neither ) . Since the study was relatively short ( 6 months follow-up ) , the primary outcome was a composite score of process quality – the quality of monitoring the variables compared to target . Secondary outcomes included clinical outcomes plus evaluations of the tracker and ATRS , and impact on health information privacy . Results : Forty-eight physicians ( mean age ( SD ) = 45.2 ( 10.0 ) , 38.2 % female ) were recruited and 511 patients ( mean age ( SD ) = 60.3 ( 12.4 ) , 49.6 % female , 78 % completed high school ) were r and omized . Only 46.1 % of patients used the Internet at least monthly so print versions of their recent information were sent to them prior to their physician visits . There were frequent technical problems with the Web-based tracker and a lack of data integration between the various EMRs and the tracker . Despite problems , the primary outcome of composite score of physician visits , and checks of blood pressure ( BP ) , LDL cholesterol , HbA1C , microalbuminuria , BMI , feet and eyes , showed a highly statistically significant improvement in the intervention group compared to control ( p<0.0001 ) . There were also highly statistically significant improvements in actual blood pressure ( -2.68 mm diastolic BP , p=0.007 ) and in HbA1C ( -.2 % , p=0.001 ) . 75.9 % of intervention patients were as satisfied or more satisfied with their care since the use of the tracker system and 62.5 % voted to continue to receive ATRS reminders . 22.4 % of patients felt that , in general , the risk of possible loss of confidentiality outweighed the benefits that computers could bring to their health . Over the course of the study , physicians developed a more favourable attitude towards the benefits vs risks of computerized systems in healthcare . Discussion : Despite considerable technical challenges for both patients and physicians , we have demonstrated that the care of a complex chronic disease can be improved with electronic tracking and decision support for both physician and patient . This is one of the first r and omized trial to demonstrate success in routine , community-based primary care . Funding Source : Grant from the Canada Health Infostructure Partnerships Program , Health Canada . References : 1 . Branger PJ . van't Hooft A. van der Wouden JC . Moorman PW . van Bemmel JH . Shared care for diabetes : supporting communication between primary and secondary care . International Journal of Medical Informatics 1999 ; 53:133 - 42 . 2 . Jerant AF . Hill DB . Does the use of electronic medical records improve surrogate patient outcomes in outpatient setting s ? Journal of Family Practice 2000;49:349 - 57 . * Dr Lee is deceased Abstract Objective To test the effectiveness of educational interventions in improving detection rates and management of dementia in primary care . Design Unblinded , cluster r and omised , before and after controlled study . Setting General practice s in the United Kingdom ( central Scotl and and London ) between 1999 and 2002 . Interventions Three educational interventions : an electronic tutorial carried on a CD Rom ; decision support software built into the electronic medical record ; and practice based workshops . Participants 36 practice s participated in the study . Eight practice s were r and omly assigned to the electronic tutorial ; eight to decision support software ; 10 to practice based workshops ; and 10 to control . Electronic and manual search es yielded 450 valid and usable medical records . Main outcome measures Rates of detection of dementia and the extent to which medical records showed evidence of improved concordance with guidelines regarding diagnosis and management . Results Decision support software ( P = 0.01 ) and practice based workshops ( P = 0.01 ) both significantly improved rates of detection compared with control . There were no significant differences by intervention in the measures of concordance with guidelines . Conclusions Decision support systems and practice based workshops are effective educational approaches in improving detection rates in dementia Advance directives name a surrogate decision maker or provide written instructions with the intent of extending patient autonomy with respect to end-of-life decisions [ 1 - 3 ] . Supported on various grounds by the public [ 1 ] , physicians [ 4 ] , ethicists [ 5 ] , and legislators [ 6 ] , advance directives have also been promoted as a way to control the high costs of health care at the end of life [ 7 , 8 ] . Most patients are interested in establishing advance directives , but few actually complete them [ 1 , 9 , 10 ] . In 1990 , the U.S. Congress passed the Patient Self-Determination Act , which requires hospitals to inform admitted patients about their right to record advance directives [ 6 , 11 ] . The Act does not dictate who should initiate these discussion s ( patients , physicians , or an admissions officer , for example ) [ 12 , 13 ] . It is therefore not surprising that the Act has had little effect on the rate of completion of advance directives [ 11 , 13 - 15 ] . Because hospitalized patients are often acutely ill and lose their ability to make decisions [ 3 ] , it may be more appropriate to discuss such issues before hospitalization [ 12 , 16 , 17 ] . Other interventions aim ed at increasing the establishment of advance directives have met with mixed success [ 18 ] . With one exception [ 19 ] , patient education has had little or no effect [ 20 - 24 ] . More effective interventions have trained physicians , social workers , or counselors to discuss advance directives [ 18 , 22 , 25 - 27 ] ; this has led to the conclusion that counseling by a clinician is the best catalyst for the completion of advance directives [ 28 ] . However , little is known about how to educate and motivate clinicians to solicit advance directives [ 28 ] . We [ 29 - 31 ] and others [ 32 ] have previously shown that computer reminders increase physician compliance with practice guidelines . In this study , we tested the hypothesis that reminding primary care physicians to discuss advance directives would stimulate such discussion s and lead to the establishment of more advance directives . Methods Setting and Patients This study was approved by the institutional review board of Indiana University as expedited research with waiver of informed consent from both patients and physicians . It was conducted in the General Medicine Practice [ 31 ] , an academic primary care practice affiliated with an urban public teaching hospital . This practice is staffed by general internal medicine faculty , fellows , and residents . Each resident and fellow attends the General Medicine Practice one half-day per week ; faculty attend one to four half-days per week . Residents always practice with the same attending faculty physicians . All physicians , except for study investigators , were eligible to participate . At the time of this study , the General Medicine Practice comprised four separate practice s with separate waiting areas , clerks , and nurses . Each practice held eight half-day sessions per week . Each session was attended by two faculty members and two or three residents , each of whom provided primary care to assigned panels of patients . Residents were required to briefly discuss each patient with the attending faculty . Fellows served as faculty and were treated as such . Since 1981 , a computerized program has r and omly assigned new physicians to the practice sessions [ 31 ] . New patients have been sequentially assigned to open appointment slots ; this result ed in no important differences in patients or clinical practice among the sessions [ 29 , 33 ] . We included patients who were at risk for acute deterioration ( and therefore might benefit from advance directives ) because of advanced age ( 75 years , the typical threshold for the oldest old ) or because they were 50 years of age or older and had one of the following chronic conditions : cardiac ischemia , heart failure , chronic lung disease , cancer other than nonmelanomatous skin cancer , cerebrovascular disease , renal insufficiency , or cirrhosis . We chose 50 years of age as a cut-off to yield sufficient numbers of patients . A computer program identified eligible patients among those with scheduled appointments at the General Medicine Practice by using problem lists and test results stored in the Regenstrief Medical Record System [ 34 ] . Eligible patients who kept appointments at the General Medicine Practice were approached by research assistants in the waiting room . The research assistants , who were blinded at all times to the patients ' study groups , explained the study to the patients , invited them to participate , and interviewed those who agreed to participate ; patients from nursing homes and prisons and patients who were deaf or did not speak English were excluded . The assistants then administered the Pfeiffer Mental Status Question naire [ 35 ] ; patients whose scores indicated cognitive dysfunction were excluded . The remaining patients provided sociodemographic information and stated whether they had previously discussed or completed advance directives ; patients who had completed advance directives were excluded . Patients also stated their preferences with regard to six treatments in the event of a terminal illness [ 36 ] . Advance Directives Before the study , we created two separate forms for instruction directives and proxy directives ; these forms became the official advance directive documents of the hospital and its outpatient services . The instruction directive allowed patients to indicate whether , in the event of terminal illness and mental incapacity , they wanted or did not want eight types of care : cardiopulmonary resuscitation , mechanical ventilation , surgery , invasive procedures , nutrition and hydration , transfusion of blood or blood products , antibiotics , or noninvasive diagnostic tests . The primary care physician had to sign each completed instruction directive form to indicate that he or she was aware of its contents . The proxy directive design ated both primary and secondary health care representatives . We placed both advance directive forms in a drawer of the desk of each physician in the General Medicine Practice . We also placed the forms in a bin near the door of the staff room along with other forms and requisitions and business reply envelopes for patients who wanted to complete the forms at home . Research assistants entered the data from completed forms into the Regenstrief Medical Record System , where the forms were available for viewing through computer terminals and workstations in all inpatient and outpatient venues [ 34 ] . Before the study , the three physician-investigators presented the basic concepts of advance directives at gr and rounds . They also had face-to-face meetings with each physician in the General Medicine Practice and explained how to complete and process the forms . We encouraged physicians to discuss advance directives with their elderly and debilitated patients and posted flyers in each practice staffing room suggesting that physicians discuss advance directives with patients who had the target study conditions . Study Methods The intent of the r and omization scheme was to expose physicians to the same type of reminder or reminders , or no reminders , during all of their scheduled primary care visits with enrolled patients . At the time of this study , 32 weekly half-day sessions took place on the four General Medicine Practice practice s. Two sessions attended by study investigators were excluded . We r and omly assigned all of the physicians who worked in a particular half-day session to the same reminder category . At the time of r and omization , 16 physicians ( all of whom were faculty members ) practice d in more than 1 session per week ( 14 practice d in 2 sessions and 2 practice d in 3 sessions ) . Therefore , we r and omly assigned the sessions in a stepped manner by first allocating the 16 physicians and all of their associated sessions to four categories : control ( no reminders ) , computer-generated reminders for instruction directives , computer-generated reminders for proxy directives , and computer-generated reminders for both types of directives . We then r and omly assigned the remaining 8 sessions and their physicians to the four categories ( Table 1 ) . Each practice contained sessions in all four categories , which were equally distributed between mornings and afternoons . Table 1 . Results of R and omization All physicians routinely received computer-generated reminders for patients with scheduled visits . They were reminded to give preventive care , note abnormal test results , and avoid drug interactions [ 29 , 34 ] . These reminders appeared at the bottom of computer-generated printed encounter forms [ 34 ] ( Figure 1 ) . Physicians routinely review ed the encounter forms and the practice chart immediately before visiting the patient . As recommended by Litzelman and coworkers [ 37 ] , the advance directive reminders were followed by a choice list ( discussed today , next visit , not applicable , patient too ill , patient refuses to discuss , I disagree with advance directives ) . Instruction directives were called advance directives , and proxies were called health care representatives ( Figure 1 ) . Figure 1 . General Medicine Practice encounter form showing reminders for both types of advance directive . After patients were enrolled , research assistants attempted to interview them in the waiting room after each scheduled appointment to assess whether they had discussed advance directives with their physicians that day . Patients who answered yes were defined as having had an advance directive discussion . During the first scheduled General Medicine Practice visit in the 5-month period between 11 and 16 months after enrollment , a close-out interview was attempted . If no scheduled visit had occurred by 15 months after enrollment , the close-out interview was attempted by telephone . Form completion was defined as having occurred if either completed form was received between study enrollment and 30 days after the final interview ( this made it possible to receive by mail forms that were completed after the close-out Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in elderly patients . Despite this , the ' rule of halves ' particularly applies to this group . We conducted a r and omised controlled trial to evaluate different levels of feedback design ed to improve identification , treatment and control of elderly hypertensives . Fifty-two general practice s were r and omly allocated to either : Control ( n=19 ) , Audit only feedback ( n=16 ) or Audit plus Strategic feedback , prioritising patients by absolute risk ( n=17 ) . Feedback was based on electronic data , annually extracted from practice computer systems . Data were collected for 265,572 patients , 30,345 aged 65 - 79 . The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced . There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group . Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control BACKGROUND Optimal care for patients with diabetes is difficult to achieve in clinical practice . OBJECTIVE To evaluate the impact of a registry and decision support system on processes of care , and physiologic control . PARTICIPANTS R and omized trial with clustering at the practice level , involving 7,412 adults with diabetes in 64 primary care practice s in the Northeast . INTERVENTIONS Provider decision support ( reminders for overdue diabetes tests , alerts regarding abnormal results , and quarterly population reports with peer comparisons ) and patient decision support ( reminders and alerts ) . MEASUREMENTS AND MAIN RESULTS Process and physiologic outcomes were evaluated in all subjects . Functional status was evaluated in a r and om patient sample via question naire . We used multiple logistic regression to quantify the effect , adjusting for clustering and potential confounders . Intervention subjects were significantly more likely to receive guideline -appropriate testing for cholesterol ( OR = 1.39 ; [ 95%CI 1.07 , 1.80 ] P = 0.012 ) , creatinine ( OR = 1.40 ; [ 95%CI 1.06 , 1.84 ] P = 0.018 ) , and proteinuria ( OR = 1.74 ; [ 95%CI 1.13 , 1.69 ] P = 0.012 ) , but not A1C ( OR = 1.17 ; [ 95 % CI 0.80 , 1.72 ] P = 0.43 ) . Rates of control of A1C and LDL cholesterol were similar in the two groups . There were no differences in blood pressure , body mass index , or functional status . CONCLUSIONS A chronic disease registry and decision support system based on easily obtainable laboratory data was feasible and acceptable to patients and providers . This system improved the process of laboratory monitoring in primary care , but not physiologic control Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure OBJECTIVE —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 whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners ( GPs ) . RESEARCH DESIGN AND METHODS A r and omized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Data base . Among these , 150 GPs ( intervention group ) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ( " high risk " ) , whereas the other 150 GPs ( control group ) received only the letter . The electronic reminder , integrated into a st and ard software system for the management of the daily clinical practice , was displayed when every participating GP opened the medical record of diabetic patients aged > or = 30 years . Only high-risk diabetic patients were included in the analysis . Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up . RESULTS We selected 15,343 high-risk diabetic patients , 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group . Overall , 1,672 patients ( 22.9 % ) of the control group and 1,886 ( 23.5 % ) patients of the intervention group received antiplatelet drugs at baseline ( P = N.S. ) . At the end of the follow-up , the number of treated patients was significantly increased in the intervention group ( odds ratio 1.99 , 95 % CI 1.79 - 2.22 ) versus the control group . The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases ( CVDs ) , compared with those with CVDs . CONCLUSIONS These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs CONTEXT Computerized systems to remind physicians to provide appropriate care have not been widely evaluated in large numbers of patients in multiple clinical setting s. OBJECTIVE To examine whether a computerized reminder system operating in multiple Veterans Affairs ( VA ) ambulatory care clinics improves resident physician compliance with st and ards of ambulatory care . DESIGN , SETTING , AND PARTICIPANTS A total of 275 resident physicians at 12 VA medical centers were r and omly assigned in firms or half-day clinic blocks to either a reminder group ( n = 132 ) or a control group ( n = 143 ) . During a 17-month study period ( January 31 , 1995-June 30 , 1996 ) , the residents cared for 12,989 unique patients for whom at least 1 of the studied st and ards of care ( SOC ) was applicable . MAIN OUTCOME MEASURES Compliance with 13 SOC , tracked using hospital data bases and encounter forms completed by residents , compared between residents in the reminder group vs those in the control group . RESULTS Measuring compliance as the proportion of patients in compliance with all applicable SOC by their last visit during the study period , the reminder group had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 58.8 % vs 53.5 % ; odds ratio [ OR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.08 - 1.42 ; P = .002 ) and for 5 of the 13 st and ards examined individually . Measuring compliance as the proportion of all visits for which care was indicated in which residents provided proper care , the reminder group also had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 17.9 % vs 12.2 % ; OR , 1.57 ; 95 % CI , 1.45 - 1.71 ; P<.001 ) and for 9 of the 13 st and ards examined individually . The benefit of reminders , however , declined throughout the course of the study , even though the reminders remained active . CONCLUSIONS Our data indicate that reminder systems installed at multiple sites can improve residents ' compliance to multiple SOC . The benefits of such systems , however , appear to deteriorate over time . Future research needs to explore methods to better sustain the benefits of reminders . JAMA . 2000;284:1411 - 1416 OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care OBJECTIVE The Diabetes Care Protocol ( DCP ) , a multifaceted computerized decision support diabetes management intervention , reduces cardiovascular risk of type 2 diabetic patients . We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective . RESEARCH DESIGN AND METHODS A cluster r and omized trial provided data of DCP versus usual care . The 1-year follow-up patient data were extrapolated using a modified Dutch microsimulation diabetes model , computing individual lifetime health-related costs , and health effects . Incremental costs and effectiveness ( quality -adjusted life-years [ QALYs ] ) were estimated using multivariate generalized estimating equations to correct for practice -level clustering and confounding . Incremental cost-effectiveness ratios ( ICERs ) were calculated and cost-effectiveness acceptability curves were created . Stroke costs were calculated separately . Subgroup analyses examined patients with and without cardiovascular disease ( CVD+ or CVD− patients , respectively ) . RESULTS Excluding stroke , DCP patients lived longer ( 0.14 life-years , P = NS ) , experienced more QALYs ( 0.037 , P = NS ) , and incurred higher total costs ( € 1,415 , P = NS ) , result ing in an ICER of € 38,243 per QALY gained . The likelihood of cost-effectiveness given a willingness-to-pay threshold of € 20,000 per QALY gained is 30 % . DCP had a more favorable effect on CVD+ patients ( ICER = € 14,814 ) than for CVD− patients ( ICER = € 121,285 ) . Coronary heart disease costs were reduced ( € −587 , P < 0.05 ) . CONCLUSIONS DCP reduces cardiovascular risk , result ing in only a slight improvement in QALYs , lower CVD costs , but higher total costs , with a high cost-effectiveness ratio . Cost-effective care can be achieved by focusing on cardiovascular risk factors in type 2 diabetic patients with a history of CVD Information Technology ( IT ) enables health care providers to manage patients with chronic conditions through identification , follow up and administration of specific interventions . In our setting , we developed a surveillance system for chronic diseases . The aim of this study was to show its efficacy on monitoring blood pressure throughout a cluster r and omized controlled trial . Patients without blood pressure registries ( condition 1 ) or with high blood pressure measurements ( condition 2 ) were r and omized to be detected by the surveillance system or to receive usual care . The proportion of patients with at least one blood pressure measurement within three months of follow up was 49.9 % ( 207 patients ) in the intervention group and 37 % ( 195 ) in the control group ( p<0.001 ) for condition 1 . And 61 % ( 224 ) vs. 50 % ( 239 ) respectively ( p=0.002 ) for condition 2 . Patients under the surveillance system have higher proportion of blood pressure measurements , showing this study an improvement on the process of care with this IT tool BACKGROUND Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor . METHODS We recruited 68 primary care family and internal medicine practice s ; 66 were r and omly allocated to a study arm ; 5 practice s withdrew , result ing in 29 receiving the Third Adult Treatment Panel ( ATP III ) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC-7 ) . The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment . All practice s received copies of each clinical practice guideline , an introductory lecture , 1 performance feedback report , and 4 visits for intervention-specific academic detailing . Data were abstract ed at 61 practice s from r and om sample s of medical records of patients treated from June 1 , 2001 , through May 31 , 2003 ( baseline ) , and from May 1 , 2004 , through April 30 , 2006 ( follow-up ) . The proportion screened with subsequent appropriate decision making ( primary outcome ) was calculated . Generalized estimating equations were used to compare results by arm , accounting for clustering of patients within practice s. RESULTS We examined 5057 baseline and 3821 follow-up medical records . The screening rate for lipid levels increased from 43.6 % to 49.0 % ( ATP III practice s ) and from 40.1 % to 50.8 % ( control practice s ) ( net difference , -5.3 % [ P = .22 ] ) . Appropriate management of lipid levels decreased slightly ( 73.4 % to 72.3 % ) in ATP III practice s and more markedly ( 79.7 % to 68.9 % ) in control practice s. The net change in appropriate management favored the intervention ( + 9.7 % ; 95 % confidence interval [ CI ] , 2.8%-16.6 % [ P < .01 ] ) . Appropriate drug prescription within 4 months decreased in both arms ( 38.8 % to 24.8 % in ATP III practice s and 45.3 % to 24.1 % in control practice s ; net change , + 7.2 % [ P = .37 ] ) Overtreatment declined from 6.6 % to 3.9 % in ATP III and rose from 4.2 % to 6.4 % in control practice s ( net change , -4.9 % [ P = .01 ] ) . CONCLUSIONS A multifactor intervention including personal digital assistant-based decision support may improve primary care physician adherence to the ATP III guidelines . Trial Registration clinical trials.gov Identifier : NCT00224848 Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake Introduction The object of this study was to examine the effect of population -based disease management and case management on re source use , self-reported health status , and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization ( HMO ) . Methods Study design consisted of a prospect i ve , r and omized controlled open trial of 18 months ' duration . Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area . Members were care managed with an expert clinical information system and frequent telephone contact . Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) , re source use measured by admission rates and bed-days per thous and per year , member satisfaction , and costs measured by paid cl aims . Results More favorable outcomes occurred in the intervention group for satisfaction with the health plan ( P < .01 ) and the social function domain as measured by SF-36 ( P = .04 ) . There was no difference in member retention or mortality between groups . Use of skilled nursing home services was significantly lower in the intervention group than in the control ( 616 vs 747 days per thous and members per year , P = .02 ) . This reduction , however , did not lead to lower mean total expenditures in the intervention group compared with the control ( $ 6828 per member for 18 months vs $ 7001 , P = .61 ) . Conclusion Population -based disease management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in re source use or improved member retention We analyze the effect of a decision support tool design ed to help physicians detect and correct medical " missteps " . The data comes from a r and omized trial of the technology on a population of commercial HMO patients . The key findings are that the new information technology lowers average charges by 6 % relative to the control group . This reduction in re source utilization was the result of reduced in-patient charges ( and associated professional charges ) for the most costly patients . The rate at which identified issues were resolved was generally higher in the study group than in the control group , suggesting the possibility of improvements in care quality along measured dimensions and enhanced diffusion of new protocol s based on new clinical evidence BACKGROUND Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease . The Computer-based Clinical Decision Support System provides an opportunity t close these gaps . OBJECTIVES To study the impact of computerized intervention on secondary prevention of CAD . METHODS The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an up date d lipoprotein profile and treatment with lipid-lowering drugs . The program produced automatic computer-generated monitoring and treatment recommendations . Adjusted primary clinics were r and omly assigned to intervention ( n=56 ) or st and ard care arms ( n=56 ) . Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment . Compliance and lipid levels were monitored . The study group comprised all patients with CAD who were alive at least 3 months after hospitalization . RESULTS Follow-up was available for 7448 patients ( median 19.8 months , range 6 - 36 months ) . Overall , 51.7 % of patients were adequately screened , and 55.7 % of patients were compliant with treatment to lower lipid level . In patients with initial low density lipoprotein > 120 mg/dl , a significant decrease in LDL levels was observed in both arms , but was more pronounced in the intervention arm : 121.9 + /- 34.2 vs. 124.3 + /- 34.6 mg/dl ( P < 0.02 ) . A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs , 37 % vs. 40.9 % ( P < 0.001 ) . CONCLUSIONS This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines , presenting a major obstacle to implementing effective secondary prevention . Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation OBJECTIVE : To improve functional status among primary care patients .INTERVENTION : 1 ) Computer-generated feedback to physicians about the patient ’s functional status , the patient ’s self-reported “ chief complaint , ” and problem-specific re source and management suggestions ; and 2 ) two brief interactive educational sessions for physicians . DESIGN : R and omized controlled trial . SETTING : University primary care clinic . PARTICIPANTS : All 73 internal medicine houseofficers and 557 of their new primary care patients . MEASURES : 1 ) Change in patient functional status from enrollment until six months later , using the Functional Status Question naire ( FSQ ) ; 2 ) management plans and additional information about functional status abstract ed from the medical record ; and 3 ) physician attitude about whether internists should address functional status problems . RESULTS : Emotional well-being scores improved significantly for the patients of the experimental group physicians compared with those of the control group physicians ( p<0.03 ) . Limitations in social activities indicated as “ due to health ” decreased among the elderly ( > 70 years of age ) individuals in the experimental group compared with the control group ( p<0.03 ) . The experimental group physicians diagnosed more symptoms of stress or anxiety than did the control group physicians ( p<0.001 ) and took more actions recommended by the feedback form ( p<0.02 ) . CONCLUSIONS : Computer-generated feedback of functional status screening results accompanied by re source and management suggestions can increase physician diagnoses of impaired emotional well-being , can influence physician management of functional status problems , and can assist physicians in improving emotional well-being and social functioning among their patients OBJECTIVE : Suboptimal treatment of hyperlipidemia in patients with coronary artery disease ( CAD ) is well documented . We report the impact of a computer-assisted physician-directed intervention to improve secondary prevention of hyperlipidemia . DESIGN AND SETTING : Two hundred thirty-five patients under the care of 14 primary care physicians in an academically affiliated practice with an electronic health record were enrolled in this proof-of-concept physician-blinded r and omized , controlled trial . Each patient with CAD or risk equivalent above National Cholesterol Education Program-recommended low-density lipoprotein ( LDL ) treatment goal for greater than 6 months was r and omized , stratified by physician and baseline LDL . Physicians received a single e-mail per intervention patient . E-mails were visit independent , provided decision support , and facilitated “ one-click ” order writing . MEASUREMENTS : The primary outcomes were changes in hyperlipidemia prescriptions , time to prescription change , and changes in LDL levels . The time spent using the system was assessed among intervention patients . RESULTS : A greater proportion of intervention patients had prescription changes at 1 month ( 15.3 % vs 2 % , P=.001 ) and 1 year ( 24.6 % vs 17.1 % , P=.14 ) . The median interval to first medication adjustment occurred earlier among intervention patients ( 0 vs 7.1 months , P=.005 ) . Among patients with baseline LDLs > 130 mg/dL , the first postintervention LDLs were substantially lower in the intervention group ( 119.0 vs 138.0 mg/dL , P=.04 ) . Physician processing time was under 60 seconds per e-mail . CONCLUSION : A visit-independent disease management tool result ed in significant improvement in secondary prevention of hyperlipidemia at 1-month postintervention and showed a trend toward improvement at 1 year CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits OBJECTIVES To evaluate the implementation of clinical guidelines for diabetes mellitus in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . METHODS R and omized study with health center as unit . General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . Seventeen health centers with 24 doctors and 499 patients with diabetes mellitus were in the intervention group and 12 health centers with 29 doctors and 535 patients were in the control group . Main outcome measures were group differences in fractions of patients without registration s ( process evaluation ) and mean group differences for the same variables ( patient outcome evaluation ) . RESULTS Statistically significant group differences were experienced for fractions of patients without registration of cigarette smoking ( intervention group , 82.6 % ; control group 94.5 % ) , body mass index ( 78.2 % vs. 93.0 % ) , and sufficient registration s for calculation of risk score for myocardial infa rct ion ( 91.1 % vs. 98.3 % ) ; all during 18 months . Large center variations were shown for all variables . The only statistically significant group difference was -2.3 mm Hg ( 95 % CI , -3.8 , -0.8 ) in diastolic blood pressure in favor of the intervention group . Statistically insignificant differences in favor of the intervention group were HbA1c , -0.1 % ( 95 % CI , -0.4 , 0.1 ) , systolic blood pressure , -1.2 mm Hg ( 95 % CI , -4.4 , 2.0 ) . Statistically insignificant differences in favor of the control group were fractions of smokers , + 3.0 % ( 95 % CI , -4.0 , 10.0 ) , body mass index , + 0.3 kg/m2 ( 95 % CI , -0.8 , 1.4 ) , risk score in female + 0.1 ( 95 % CI , -5.1 , 5.2 ) , and risk score in male + 2.6 ( 95 % CI , -14.2 , 19.5 ) . CONCLUSIONS Implementation of clinical guidelines for diabetes mellitus in general practice , by means of a CDSS and several procedures for implementation , did not result in a clinical ly significant change in doctors ' behavior or in patient outcome PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care BACKGROUND Less than one third of the 65 million Americans with hypertension have adequate blood pressure ( BP ) control . This study examined the effectiveness of 2 interventions for improving patient BP control . METHODS This was a 2-level ( primary care provider and patient ) cluster r and omized trial with 2-year follow-up occurring among patients with hypertension enrolled from a Veterans Affairs Medical Center primary care clinic . Primary care providers ( n = 17 ) in the intervention received computer-generated decision support design ed to improve guideline concordant medical therapy at each visit ; control providers ( n = 15 ) received a reminder at each visit . Patients received usual care or a bimonthly tailored nurse-delivered behavioral telephone intervention to improve hypertension treatment . The primary outcome was proportion of patients who achieved a BP < 140/90 mm Hg ( < 130/85 for diabetic patients ) over the 24-month intervention . RESULTS Of the 816 eligible patients contacted , 190 refused and 38 were excluded . The 588 enrolled patients had a mean age of 63 years , 43 % had adequate baseline BP control , and 482 ( 82 % ) completed the 24-month follow-up . There were no significant differences in amount of change in BP control in the 3 intervention groups as compared to the hypertension reminder control group . In secondary analyses , rates of BP control for all patients receiving the patient behavioral intervention ( n = 294 ) improved from 40.1 % to 54.4 % at 24 months ( P = .03 ) ; patients in the nonbehavioral intervention group improved from 38.2 % to 43.9 % ( P = .38 ) , but there was no between-group differences at the end of the study . CONCLUSION The brief behavioral intervention showed improved outcomes over time , but there were not significant between group differences Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p < 0.001 ) ; 61.7 % ( 156/253 ) of patients in the intervention group , compared with 42.6 % ( 110/258 ) of control patients , showed improvement ( difference 19.1 % , p < 0.001 ) . The clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 . OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested . Sixty family physicians were r and omised to two treatment strategies . " Test " physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing . Computer feedback on management was mailed to the doctors . This encouraged doctors to apply the " stepped care " protocol , supplied charts of diastolic blood pressure v time , and ranked patients ' diastolic blood pressures by percentile . Letters were mailed to patients to remind them of appointments . " Control " doctors filled out the same data collection forms as test physicians , but neither doctors nor patients received computer feedback . Physicians who used the computer saw more patients per practice than control doctors ( test 50 patients , control 40 ) . For all patients the length of follow up was significantly longer in test practice s ( test 199 days , control 167 ) , and a smaller percentage dropped out of active treatment in test practice s ( test 37.5 % , control 42.1 % ) . For patients with " moderate " hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practice s ( 88.5 mm Hg ) , but it failed to reach this goal in control practice s ( 93.3 mm Hg ) . A greater average reduction of diastolic pressure was achieved in test practice s ( test 21.7 mm Hg , control 16.7 mm Hg ) . Though patients with " moderate " hypertension were better controlled in test practice s than in control practice s , the patients in test practice s visited their doctors less often ( test 13.3 visits per patient-year , control 17.4 visits ) . Among patients with newly detected hypertension test practice s achieved a greater reduction in diastolic pressure than control practice s ( test 15.1 mm Hg v control 11.3 mm Hg ) and more sustained control of hypertension ( test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days ) AIMS The Diabetes Care Protocol ( DCP ) combines task delegation , intensification of diabetes treatment and feedback . It reduces cardiovascular risk in Type 2 diabetes ( T2DM ) patients . This study determines the effects of DCP on patient-important outcomes . METHODS A cluster r and omized , non-inferiority trial , by self-administered question naires in 55 Dutch primary care practice s : 26 practice s DCP ( 1699 patients ) , 26 usual care ( 1692 patients ) . T2DM patients treated by their general practitioner were included . Main outcome was the 1-year between-group difference in Diabetes Health Profile ( DHP-18 ) total score . SECONDARY OUTCOMES DHP-18 subscales , general perceived health [ Medical Outcomes Study 36-Items Short Form Health Survey ( SF-36 ) , Euroqol 5 Dimensions ( EQ-5D ) and Euroqol visual analogue scale ( EQ-VAS ) ] , treatment satisfaction ( Diabetes Treatment Satisfaction Question naire ; DTSQ status ) and psychosocial self-efficacy ( Diabetes Empowerment Scale Short Form ; DES-SF ) . Per protocol ( PP ) and intention-to-treat ( ITT ) analyses were performed : non-inferiority margin Delta=-2 % . At baseline 2333 question naires were returned and 1437 1 year thereafter . RESULTS Comparing DCP with usual care , DHP-18 total score was non-inferior : PP -0.88 ( 95 % CI -1.94 to 0.12 ) , ITT -0.439 ( 95 % CI -1.01 to 0.08 ) , SF-36 ' health change ' improved : PP 3.51 ( 95 % CI 1.23 to 5.82 ) , ITT 1.91 ( 95 % CI 0.62 to 3.23 ) , SF-36 ' social functioning ' was inconclusive : PP-1.57 ( 95 % CI-4.3 to 0.72 ) , ITT-1.031 ( 95 % CI-2.52 to -0.25 ) . Other DHP and SF-36 scores were inconsistent or non-inferior . DHP-18 ' disinhibited eating ' was significantly worse in PP analyses . For EQ-5D/EQ-VAS , DTSQ and DES-SF , no significant between-group differences were found . CONCLUSION DCP does not seem to influence health status negatively , therefore diabetes care providers should not shrink from intensified treatment . However , they should take possible detrimental effects on ' social functioning ' and ' disinhibited eating ' into account Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines . Very little has been published about the use of computerized reminders for preventive care in diabetes . We implemented a computer-generated reminder system for diabetes care guidelines in a r and omized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals . After a six month study period , compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines ( 38.0 % at baseline , 54.9 % at follow-up ) and the control group that received a nonspecific report ( 34.6 % at baseline , 51.0 % at follow-up ) . There was no significant difference between the two groups . Both clinic sites showed similar improvement over baseline levels of compliance . Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms ( 19.7 % vs. 7.6 % , p = 0.006 ) . The improvements in guideline compliance were seen in all areas of diabetes preventive care studied , and significant improvements were seen with recommended items from the medical history , physical exam , laboratory testing , referrals , and patient education . The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care . These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status . Further study is needed to underst and the implication s of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P<.001 ) . The effect of provider advice combined with patient education was not significantly different from provider advice alone ( P=.88 ) . Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients Interventions that have proven effective in the management of chronic illness have often been difficult to establish in widespread practice . The Chronic Care Model provides a framework for implementing interventions , but it is expensive and difficult to implement . We developed a decision support system based on this model to improve the care of adults who have diabetes and receive primary care in Vermont or adjacent New York . The Vermont Diabetes Information System uses a network of community laboratories for providing data to produce flowsheets , reminders , action alerts , and population reports that are sent to primary care providers by fax and to patients by mail . Currently , 7295 patients are cared for by 124 primary care providers in 62 practice s and are enrolled in a r and omized controlled trial to study its effects BACKGROUND AND OBJECTIVE To assess the cost-effectiveness of an intervention based on the Global INitiative for Asthma ( GINA ) recommendations as compared to usual care . SUBJECTS AND METHOD Pragmatic , cluster-r and omised trial . Ten pneumologists and 10 general practitioners were r and omised to an intervention or control group , recruiting 98 and 100 asthma patients , respectively . The intervention consisted of an education program and a clinical decision support system ( CDSS ) providing recommendations based on the GINA . The control group was characterized by usual care . Effectiveness was assessed by the health related quality of life as measured by the St. George 's Respiratory Question naire ( SGRQ ) . Costs were computed from the re source consumption recorded during a 12 months follow-up period , and the cost-effectiveness of the intervention was investigated in an incremental analysis . RESULTS The intervention effect on the SGRQ total score was estimated as a 6.8 point reduction ( 95 % confidence interval , 2.5 - 11.1 ; p = 0.0021 ) , and a significant improvement in the SGRQ subscores and in the symptoms-free periods were also observed . From the social perspective , the mean total costs showed savings of -1,022 Euros ( 95 % confidence interval , -2,165 to 122 ; p = 0.0795 ) in intervention group as compared to usual care . The incremental analysis confirmed that the intervention was cost-effective . CONCLUSIONS The implementation of an asthma management program based in GINA recommendations improved the patient 's health related quality of life and was cost-effective as compared to usual care Clinical decision support systems ( CDSSs ) differ from other health information systems in their aim to directly influence the decision-making behaviour of healthcare professionals . As a result , CDSSs face additional challenges with respect to user acceptance . The objective of this study was to investigate subjective usability of a guideline -based CDSS for outpatient cardiac rehabilitation . The system , named CARDSS , was previously found to be effective in improving guideline adherence of rehabilitation professionals in a cluster r and omized trial . To assess CARDSS ' usability , a modified version of the IBM Computer System Usability Question naire was sent to all 68 professionals from the 28 outpatient clinics that participated in the trial . The question naire was returned by 63 respondents ( 93 % ) from 27 clinics . Factors that influenced CARDSS ' usability were identified using linear regression analysis . Analysis showed that professionals who managed to smoothly integrate the system with their daily routine were more satisfied with ease of system use . Furthermore , a positive attitude of respondents towards CDSSs in general and a better agreement with the content of the national guidelines were positively correlated to satisfaction with CARDSS ' overall usability and each of its sub-domains Objective : To evaluate a computerized scheduling model that employs nonlinear optimization to recommend optimal follow-up intervals for patients taking warfarin . Design : R and omized trial . Setting : 5 anticoagulation clinics . Patients / participants : 620 patients expected to receive warfarin for ≥6 weeks . Interventions : Computer-generated recommendations for scheduling the next visit were presented to or withheld from practitioners . Measurements and main results : The main outcome measures were the follow-up interval scheduled by the provider , the interval at which the patient actually returned to clinic , and the quality of anticoagulation control ( computed as the absolute difference between the measured and target prothrombin times [ PTRs ] or international normalized ratios [ INRs ] ) . Follow-up intervals scheduled for the patients whose practitioners received computer-generated recommendations were significantly longer than those for control patients ( mean , 4.4 vs 3.5 weeks , p<0.001 ) , despite the fact that the practitioners modified the suggested return interval by > 1 week on 40 % of the visits . The interval at which the intervention group actually returned to clinic was also longer ( mean , 4.4 vs 4.1 weeks , p<0.05 ) , even though the control patients tended to return at longer intervals than were scheduled by their practitioners . Control of anticoagulation was nearly the same among experimental and control patients . Life-threatening complications occurred in the care of three experimental patients and one control patient , while other serious complications occurred in the care of 16 experimental patients and 17 control patients . Conclusions : Recommendations based on nonlinear optimization prompted clinicians to schedule less frequent follow-up for patients taking warfarin , with no deterioration in anticoagulation control . This approach to scheduling can potentially reduce utilization while maintaining quality of care for patients who require long-term monitoring We describe the design and implementation of a clinical decision support system for ambulatory hyperlipidemia management . Despite readily available and evidence -based guidelines , cholesterol control remains persistently sub-optimal in clinical practice . " FastTrack " is an integrated , multi-faceted informatics tool to reduce barriers to effective cholesterol management by proactively integrating pertinent clinical information , evidence -based decision support and a simple means to act via a single FastTrack e-mail . We tested the intervention in a r and omized , controlled trial involving 14 physicians and 276 patients . In an interim analysis , we found that physicians on average were able to review and act upon 9 patient e-mails in less than 15 minutes . Significantly more intervention patients were initiated on a statin therapy or had their dose increased ( 15.3 % vs. 2.3 % , p < 0.001 ) . Impact of the intervention on LDL levels will be assessed at trial completion The Personal Digital Assistance for Guideline Adherence ( GLAD Heart ) study was design ed to test a strategy to improve quality of care through increased adherence to ATPIII cholesterol guidelines . This paper describes the overall study design including the multi-faceted intervention and outcome measures . Sixty-one primary care practice s in NC were recruited and r and omized to either a personal digital assistant-based cholesterol management intervention or an intervention similar in intensity and frequency of contact but focused on a hypertension clinical practice guideline . Installation and implementation of the technology intervention was challenging . Over the course of the study , there were 74 technical issues requiring assistance for the palm pilot from 23 participating practice s. The GLAD Heart project was completed successfully with some impact on cholesterol management . Technology has the potential to improve the quality of care provided in the healthcare setting . However , potentially expensive interventions such as that conducted in GLAD Heart should undergo rigorous testing to assure their efficacy before widespread adoption OBJECTIVES To provide physicians with evidence -based recommendations for care at the point of service , using an automated system , and to evaluate its effectiveness in promoting prescriptions to prevent cardiovascular events . STUDY DESIGN R and omized controlled trial . METHODS Patients at risk for cardiovascular events who might benefit from angiotensin-converting enzyme inhibitors or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) were identified from electronic data in a managed care organization and r and omly assigned into 2 groups . Physicians seeing out patients in the intervention group were faxed a sheet with pertinent patient data , including a recommendation to prescribe the indicated medication . In the control group , the data sheet did not include the recommendation . Dispensed prescriptions were compared between groups . RESULTS More than 4000 visits were observed for each medication type . Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were dispensed in 7.1 % of visits in the intervention group versus 5.7 % in the control group ( P = .048 ) following the first patient-physician encounter . No significant difference was observed for statins ( intervention , 8.1 % vs control , 7.7 % ) . Data for all patient-physician encounters and both medications were combined in logistic regression analysis . The odds ratio was 1.19 for a dispensed prescription in the intervention group and 1.54 for 2 or more visits versus 1 visit . CONCLUSIONS An automated system that provides pertinent data and tailored recommendations for care at the point of service modestly increased prescription dispensing rates . Targeting patient-provider encounters to change provider behavior is challenging ; however , even small effects can produce clinical ly important results over time OBJECTIVE To test the effectiveness of two interventions design ed to improve the adoption of evidence -based practice s by home health nurses caring for heart failure ( HF ) patients . DATA SOURCES / STUDY SETTING Information on nurse practice s was abstract ed from the clinical records of patients admitted between June 2000 and November 2001 to the care of 354 study nurses at a large , urban , nonprofit home care agency . STUDY DESIGN The study employed a r and omized design with nurses assigned to usual care or one of two intervention groups upon identification of an eligible patient . The basic intervention was a one-time e-mail reminder highlighting six HF-specific clinical recommendations . The augmented intervention consisted of the initial e-mail reminder supplemented by provider prompts , patient education material , and clinical nurse specialist outreach . DATA COLLECTION At each home health visit provided by a study nurse to an eligible HF patient during the 45-day follow-up period , a structured chart abstract ion tool was used to collect information on whether the nurse provided the care practice s highlighted in the e-mail reminder . PRINCIPAL FINDINGS Both the basic and the augmented interventions greatly increased the practice of evidence -based care , according to patient records , in the areas of patient assessment and instructions about HF disease management . While not all results were statistically significant at conventional levels , intervention effects were positive in virtually all cases and effect magnitudes frequently were large . CONCLUSIONS The results of this r and omized trial strongly support the efficacy of just-in-time evidence -based reminders as a means of changing clinical practice among home health nurses who are geographically dispersed and spend much of their time in the field BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P < 0.001 ) ; the effects of the intervention remained after multivariable adjustment ( odds ratio [ OR ] 1.39 [ CI , 1.13–1.72 ] ) and the effects of the intervention did not differ by patients ’ race and ethnicity . CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma OBJECTIVE : The goal was to assess the impact of influenza vaccine clinical alerts on missed opportunities for vaccination and on overall influenza immunization rates for children and adolescents with asthma . METHODS : A prospect i ve , cluster-r and omized trial of 20 primary care sites was conducted between October 1 , 2006 , and March 31 , 2007 . At intervention sites , electronic health record-based clinical alerts for influenza vaccine appeared at all office visits for children between 5 and 19 years of age with asthma who were due for vaccine . The proportion of captured immunization opportunities at visits and overall rates of complete vaccination for patients at intervention and control sites were compared with those for the previous year , after st and ardization for relevant covariates . The study had > 80 % power to detect an 8 % difference in the change in rates between the study and baseline years at intervention versus control practice s. RESULTS : A total of 23 418 visits and 11 919 children were included in the study year and 21 422 visits and 10 667 children in the previous year . The majority of children were male , 5 to 9 years of age , and privately insured . With st and ardization for selected covariates , captured vaccination opportunities increased from 14.4 % to 18.6 % at intervention sites and from 12.7 % to 16.3 % at control sites , a 0.6 % greater improvement . St and ardized influenza vaccination rates improved 3.4 % more at intervention sites than at control sites . The 4 practice s with the greatest increases in rates ( ≥11 % ) were all in the intervention group . Vaccine receipt was more common among children who had been vaccinated previously , with increasing numbers of visits , with care early in the season , and at preventive versus acute care visits . CONCLUSIONS : Clinical alerts were associated with only modest improvements in influenza vaccination rates BACKGROUND The success of guidelines depends largely on effective implementation and uptake in clinical practice . The Optimal Renal Anemia Management Assessment ( ORAMA ) study investigated the impact of European Best Practice Guideline ( EBPG ) prompting on patient outcomes . METHODS ORAMA was a prospect i ve , international , multicenter , cluster-r and omized study . Fifty-three centers in eight European countries enrolled patients with chronic kidney disease stage V receiving chronic dialysis . Patients were either anemic ( hemoglobin [ Hb ] < 11 g/dL [ 110 g/L ] ) or treated with erythropoiesis stimulating agents and /or iron supplementation . Centers were r and omized to two groups , with or without access to a computerized clinical decision support ( CDS ) system . In a post hoc analysis , patients were further subdivided into adherence or non-adherence of investigators to the EBPG regardless of CDS usage . Primary endpoint was the proportion of patients with Hb > 11 g/ dL ( 110 g/L ) , reflecting hematological targets in the revised EPBG . RESULTS In this population of 599 dialysis patients , hematological targets did not differ in the presence or absence of a CDS system . There was a general shift towards improved patient distribution by Hb categories while the width of the distribution curves remained unchanged . The proportion of patients with Hb > 11 g/dL ( 110 g/L ) was higher among adherers ( 79 % and 84 % with or without CDS use , respectively ) than non-adherers ( 59 % and 57 % , respectively ) . CONCLUSIONS ORAMA is the first international study to show that adherence to EBPG improved attainment of anemia indices . The availability of a CDS system did not affect anemia management This study describes the influence of a computerized medical record summary system in three disease areas ( hypertension , obesity and renal disease ) observed in the course of a controlled , r and omized and prospect i ve study of 479 Northwestern University Clinic patients . Experimental patients , who had available automated record summaries , and control patients , who had available only the manual record , were compared on several medical tests and procedures whose yearly occurrence was considered good medical practice for this patient population , and were compared as well on several measures of outcome of medical care . Evidence suggesting better care and outcome of care among patients with computerized record summaries available is presented STUDY OBJECTIVE To assess the effects of evidence -based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system . DESIGN R and omized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions , which result ed in four groups of patients : physician intervention only , pharmacist intervention only , intervention by physician and pharmacist , and intervention by neither physician nor pharmacist ( control ) . SETTING Academic primary care internal medicine practice . SUBJECTS Seven hundred twelve patients with uncomplicated hypertension . MEASUREMENTS AND MAIN RESULTS Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions . The primary end point was generic health-related quality of life . Secondary end points were symptom profile and side effects from antihypertensive drugs , number of emergency department visits and hospitalizations , blood pressure measurements , patient satisfaction with physicians and pharmacists , drug therapy compliance , and health care charges . In the control group , implementation of care changes in accordance with treatment suggestions was observed in 26 % of patients . In the intervention groups , compliance with suggestions was poor , with treatment suggestions implemented in 25 % of patients for whom suggestions were displayed only to pharmacists , 29 % of those for whom suggestions were displayed only to physicians , and 35 % of the group for whom both physicians and pharmacists received suggestions ( p=0.13 ) . Intergroup differences were neither statistically significant nor clinical ly relevant for generic health-related quality of life , symptom and side-effect profiles , number of emergency department visits and hospitalizations , blood pressure measurements , charges , or drug therapy compliance . CONCLUSION Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension Discrepancies between clinical guidelines and clinical practice call for practical implementation strategies . This study evaluates the implementation of clinical guidelines for hypertension in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . We carried out a r and omized study of general practice health centres in Sør- and Nord-Trøndelag counties in Norway ( population 380000 ) . A total of 17 health centres were included , with 24 doctors and 984 patients in the intervention group . Data from 887 patients was used in the analyses . There were 12 health centres with 29 doctors and 1255 patients in the control group . Data from 1127 control patients was used in the analyses . The main outcome measures were doctor 's behaviour , measured by adherence to registration of recommended variables in the Norwegian clinical guidelines for hypertension . The aim of the intervention was to lower the fractions of patients without registration s. However , there were no clinical ly significant differences between the intervention group and the control group for fractions of patients without registration of blood pressure ( intervention group 14.3 % , control group 14.2 % ) or serum cholesterol ( 62.3 % vs. 56.8 % ) during 12 months , nor , during 18 months , for fractions of patients without a registration of cigarette smoking ( 82.9 % vs. 87.1 % ) , cardiovascular inheritance ( 79.5 % vs. 73.4 % ) and body mass index ( 81.5 % vs. 89.2 % ) . One or several variables necessary for calculation of risk score for myocardial infa rct ion were missing in 91.7 % of patients in the intervention group and 91.9 % of patients in the control group . Large centre variations were shown for all variables . Implementation of clinical guidelines in the treatment of hypertensive patients in general practice , by means of a CDSS and several procedures for implementation did not result in clinical ly significant changes in the doctors ' behaviour . Of importance are both the lack of user-friendliness of the specific CDSS and problems in performing time-consuming multidimensional procedures The present study examined the influence of a computerized medical record summary system on incidence and length of hospitalization . Additional indicators of process of care were also considered . A prospect i ve , r and omized design was used where 241 experimental patients had a computerized medical record summary and 238 control patients had the traditional medical record . All patients were followed and compared over a two-year period . Although no difference in incidence of hospitalization was found between patients with and without the summary , during the second year , patients with summaries spent fewer days in the hospital . Patients with summaries also had more completed referrals for consultation , assigned diets , detected new problems and diagnostic tests on record than patients without the summary Objective To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic . Design A r and omized trial . Setting The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System , Seattle Division . Patients / Participants Clinic providers were r and omized to a control group ( n=35 ) or intervention group ( n=36 ) . We targeted the providers of patients being treated for hypertension with calcium channel blockers , a class of drug not recommended for initial therapy . InterventionAn automated computer query identified eligible patients and their providers . A guideline reminder was placed in the charts of patients of intervention providers ; the charts of patients of control providers received no reminder . Measurements and main results During the 5-month study period , 346 patients were seen by the 36 primary care providers ( staff physicians , nurse practitioners , residents , and fellows ) in the intervention group , and 373 patients were seen by the 35 providers in the control group . Intervention providers changed 39 patients ( 11.3 % ) to other medications during the study period , compared with 1 patient ( < 1.0 % ) of control providers ( p<.0001 ) . For patients whose therapy was unchanged , providers noted angina in 23.1 % , indications other than those for hypertension in 9.5 % , intolerable adverse effects with first-line therapy in 13.9 % , and inadequte control with first-line therapy in 13.9 % . Of those patients without provider-indicated contraindications , 23.6 % were switched from calcium channel blockers to first-line agents during the intervention period . Conclusions The use of a computerized , clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general , and decreased the use of calcium channel blockers for the treatment of hypertension in particular Abstract One hundred and sixteen patients with hypertension were allocated r and omly to treatment by a computer program or by physicians . All were under the care of physicians in one of two hypertension clinics , but for computer treated patients ( C ) the program provided physicians with treatment recommendations which they were free to follow or reject whereas no recommendations were made for physician treated patients ( P ) . The computer program could use thiazide , alphamethyldopa , hydralazine or quanethidine ; physicians used whatever drugs they wished . Blood pressure ( BP ) response was similar for both groups , as were drug side effects and overt non-compliance with treatment . A computer program such as this one could guide allied health workers in setting s where expert physicians are scarce , improving large scale treatment of hypertension BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant AIM To assess the impact of two modes of spirometry expert support on Family physicians ' ( FPs ' ) diagnoses and planned management in patients with apparent respiratory disease . METHOD A cluster-r and omised trial was performed with family practice s as the unit of r and omisation . FPs from 44 family practice s recorded their diagnosis and planned management before and after spirometry for 868 patients . Intervention consisted of spirometry interpretation support by either a chest physician or expert software . Both interventions were compared with usual care ( i.e. no additional interpretation support ) . Change in FPs ' diagnoses after spirometry served as the primary outcome . Secondary outcomes were referral rate , additional diagnostic tests , and disease management changes . Effects were expressed as percentages and Odds Ratios ( OR ) with 95 % confidence intervals . RESULTS Diagnoses changed after intervention in all groups : 47.8 % ( 95 % CI 41.8 to 53.9 ) for chest physician support ; 45.0 % ( 95 % CI 39.5 to 50.6 ) for software support ; and 53.3 % ( 95 % CI 47.2 to 59.4 ) for usual care . Differences in the proportions of changed diagnosis were not statistically significant : chest physician support versus usual care OR 0.79 ( 95%CI 0.49 to 1.30 ) ; software support versus usual care OR 0.72 ( 95 % CI 0.45 - 1.15 ) . There were no differences in secondary outcomes . CONCLUSION Neither chest physician spirometry support nor expert software spirometry support had a significant impact on FPs ' diagnosis of respiratory conditions or management decisions . TRIAL NUMBER http://www . clinical trials.gov/ct/show/NCT00131157?order=1 |
443 | 27,188,734 | However , meta-regression analysis did not find the source of heterogeneity in which the publication country and follow up time were the influencing factors .
Available evidence suggests some clinical benefits of HCT combined with immunotherapy on MS . | Multiple sclerosis ( MS ) is thought to be a serious autoimmune disease .
However , few therapy method was efficient for MS .
The hematopoietic cell transplant ( HCT ) has been reported for a long time and can be used for MS .
The clinical trials consisted of small sample s and gave confusing results .
This systematic review and meta- analysis aims to estimate the effects of HCT for adults with MS . | The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy ( HDIT ) followed by autologous hematopoietic cell transplantation ( AHCT ) in advanced multiple sclerosis ( MS ) . TBI , CY and antithymocyte globulin were followed by transplantation of autologous , CD34-selected PBSCs . Neurological examinations , brain magnetic resonance imaging and cerebrospinal fluid ( CSF ) for oligoclonal b and s ( OCB ) were serially evaluated . Patients ( n=26 , mean Exp and ed Disability Status Scale (EDSS)=7.0 , 17 secondary progressive , 8 primary progressive , 1 relapsing/remitting ) were followed for a median of 48 months after HDIT followed by AHCT . The 72-month probability of worsening ⩾1.0 EDSS point was 0.52 ( 95 % confidence interval , 0.30–0.75 ) . Five patients had an EDSS at baseline of ⩽6.0 ; four of them had not failed treatment at last study visit . OCB in CSF persisted with minor changes in the b and ing pattern . Four new or enhancing lesions were seen on MRI , all within 13 months of treatment . In this population with high baseline EDSS , a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant . Non-inflammatory events may have contributed to neurological worsening after treatment . HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS . We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion . Median EDSS and SNRS scores at the time of inclusion were 6.5 ( 6.5–7.5 ) and 56 ( 44–65 ) , respectively . PBPC mobilisation was safe with no serious adverse effects , and without significant aggravation of disability . One patient improved significantly ( by 1.0 point on EDSS ) after the mobilisation . Two mobilisation failures were observed . No life-threatening events occurred during the transplantation . All grafted patients , except one , at least stabilised their disability status . One patient improved significantly ( by 1.5 points on EDSS ) , two patients improved slightly ( by 0.5 points on EDSS ) , one patient worsened by 1.0 point on the EDSS in 10 months . Improvement occurred with a delay of 2–4 months . Median EDSS and SNRS of grafted patients at the last follow up were 6.5 ( 5.5–8.5 ) and 64 ( 39–73 ) , respectively with median follow-up of 8.5 months . Further follow-up is needed to determine the disease course after complete immune reconstitution . Bone Marrow Transplantation ( 2000 ) 25 , 525–531 Clinical trials have indicated that autologous hematopoietic stem cell transplantation ( HSCT ) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis ( MS ) , but the mechanism has remained unclear . To underst and whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire , we examined the long-term immune reconstitution in patients with MS who received HSCT . After numeric recovery of leukocytes , at 2-yr follow-up there was on average a doubling of the frequency of naive CD4 + T cells at the expense of memory T cells . Phenotypic and T cell receptor excision circle ( TREC ) analysis confirmed a recent thymic origin of the exp and ed naive T cell subset . Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy . These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment IMPORTANCE Most patients with relapsing-remitting ( RR ) multiple sclerosis ( MS ) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability . High-dose immunosuppressive therapy ( HDIT ) with autologous hematopoietic cell transplant ( HCT ) may , in contrast , induce sustained remissions in early MS . OBJECTIVE To evaluate the safety , efficacy , and durability of MS disease stabilization through 3 years after HDIT/HCT . DESIGN , SETTING , AND PARTICIPANTS Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis ( HALT-MS ) is an ongoing , multicenter , single-arm , phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling . Participants are evaluated through 5 years after HCT . This report is a prespecified , 3-year interim analysis of the trial . Thirty-six patients with RRMS from referral centers were screened ; 25 were enrolled . INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34 + selected ; the participants then received high-dose treatment with carmustine , etoposide , cytarabine , and melphalan as well as rabbit antithymocyte globulin before autologous HCT . MAIN OUTCOMES AND MEASURES The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes : ( 1 ) confirmed loss of neurologic function , ( 2 ) clinical relapse , or ( 3 ) new lesions observed on magnetic resonance imaging . Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events . RESULTS Grafts were collected from 25 patients , and 24 of these individuals received HDIT/HCT . The median follow-up period was 186 weeks ( interquartile range , 176 - 250 ) weeks ) . Overall event-free survival was 78.4 % ( 90 % CI , 60.1%-89.0 % ) at 3 years . Progression-free survival and clinical relapse-free survival were 90.9 % ( 90 % CI , 73.7%-97.1 % ) and 86.3 % ( 90 % CI , 68.1%-94.5 % ) , respectively , at 3 years . Adverse events were consistent with expected toxic effects associated with HDIT/HCT , and no acute treatment-related neurologic adverse events were observed . Improvements were noted in neurologic disability , quality -of-life , and functional scores . CONCLUSIONS AND RELEVANCE At 3 years , HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function . Treatment was associated with few serious early complications or unexpected adverse events BACKGROUND Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression . We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis ( MS ) who had not responded to treatment with interferon beta . METHODS Eligible patients had relapsing-remitting MS , attended Northwestern Memorial Hospital , and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months , or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse . Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 microg per kg per day filgrastim . The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin . Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation . We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation . FINDINGS Between January , 2003 , and February , 2005 , 21 patients were treated . Engraftment of white blood cells and platelets was on median day 9 ( range day 8 - 11 ) and patients were discharged from hospital on mean day 11 ( range day 8 - 13 ) . One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster . Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with st and ard therapy . 17 of 21 patients ( 81 % ) improved by at least 1 point on the Kurtzke exp and ed disability status scale ( EDSS ) , and five patients ( 24 % ) relapsed but achieved remission after further immunosuppression . After a mean of 37 months ( range 24 - 48 months ) , all patients were free from progression ( no deterioration in EDSS score ) , and 16 were free of relapses . Significant improvements were noted in neurological disability , as determined by EDSS score ( p<0.0001 ) , neurological rating scale score ( p=0.0001 ) , paced auditory serial addition test ( p=0.014 ) , 25-foot walk ( p<0.0001 ) , and quality of life , as measured with the short form-36 ( SF-36 ) question naire ( p<0.0001 ) . INTERPRETATION Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits , but these results need to be confirmed in a r and omised trial High-dose immunosuppressive therapy ( HDIT ) with autologous hematopoietic stem cell transplantation ( AHSCT ) is a promising approach to treatment of multiple sclerosis ( MS ) patients . In this paper , we present the long-term outcomes of a prospect i ve single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients : mean age—35 years old ; male/female—39/60 ; median Exp and ed Disability Status Scale ( EDSS ) = 3.5 ; 43 relapsing/remitting MS , 56 progressive MS . No transplant-related deaths were observed . The mobilization and transplantation procedures were well tolerated . At 6 months post-transplant , neurological improvement or stabilization was observed in all the patients except one . Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT . Estimated event-free survival at median follow-up of 48.9 months was 80 % : 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS . Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis . At the median long-term follow-up of 62 months , 47 % of patients improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up ; 45 % of patients were stable . No active , new , or enlarging lesions on magnetic resonance imaging were registered in patients without disease progression . AHSCT was accompanied by a significant improvement in patient ’s quality of life . Due to the fact that patient selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous , comparison with the results in the literature should be done with caution . Thus , the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population of MS patients is very favorable . The consistency of our long-term clinical and quality of life results , together with the persistence of improvement , is in favor of the efficacy and safety of this treatment approach in MS patients OBJECTIVE To explore the safety and effectiveness of high-dose cyclophosphamide ( HiCy ) without bone marrow transplantation in patients with aggressive multiple sclerosis ( MS ) . DESIGN A 2-year open-label trial of patients with aggressive relapsing-remitting multiple sclerosis ( RRMS ) given an immunoablative regimen of HiCy ( 50 mg/kg/d for 4 consecutive days ) with no subsequent immunomodulatory therapy unless disease activity reappeared that required rescue therapy . SETTING The Johns Hopkins University Multiple Sclerosis Center , Baltimore , Maryl and . Patients A total of 21 patients with RRMS were screened for eligibility and 9 patients were enrolled in the trial . Patients were required to have 2 or more gadolinium-enhancing lesions on each of 2 pretreatment magnetic resonance imaging scans , at least 1 clinical exacerbation in the 12 months prior to HiCy treatment , or a sustained increase of 1.0 point or higher on the Exp and ed Disability Status Scale ( EDSS ) in the preceding year . Intervention Patients received 50 mg/kg/d of cyclophosphamide intravenously for 4 consecutive days , followed by 5 mug/kg/d of granulocyte colony-stimulating factor 6 days after completion of HiCy treatment , until the absolute neutrophil count exceeded 1.0 x 10(9 ) cells/L for 2 consecutive days . MAIN OUTCOME MEASURES The primary outcome of the study was the safety and tolerability of HiCy in patients with RRMS . Secondary outcome measures included a change in gadolinium-enhancing lesions on magnetic resonance images and a change in disability measures ( EDSS and Multiple Sclerosis Functional Composite ) . RESULTS Nine patients were treated and followed up for a mean period of 23 months . Eight patients had failed conventional therapy and 1 was treatment naive . The median age at time of entry was 29 years ( range , 20 - 47 years ) . All patients developed transient total or near-total pancytopenia as expected , followed by hematopoietic recovery in 10 to 17 days , stimulated by granulocyte colony-stimulating factor . There were no deaths or unexpected serious adverse events . There was a statistically significant reduction in disability ( EDSS ) at follow-up ( mean [ SD ] decrease , 2.11 [ 1.97 ] ; 39.4 % ; P = .02 ) . The mean ( SD ) number of gadolinium-enhancing lesions on the 2 pretreatment scans were 6.5 ( 2.1 ) and 1.2 ( 2.3 ) at follow-up ( 81.4 % reduction ; P = .01 ) . Two patients required rescue treatment with other immunomodulatory therapies during the study owing to MS exacerbations . CONCLUSION Treatment with HiCy was safe and well tolerated in our patients with MS . Patients experienced a pronounced reduction in disease activity and disability after HiCy treatment . This immunoablative regimen of cyclophosphamide for patients with aggressive MS is worthy of further study and may be an alternative to bone marrow transplantation . Published online June 9 , 2008 ( doi:10.1001/archneurol.65.8.noc80042 ) Multiple sclerosis ( MS ) is a disease of the central nervous system characterized by immune-mediated destruction of myelin . In patients with progressive deterioration , we have intensified immunosuppression to the point of myeloablation . Subsequently , a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells ( HSC ) . Three patients with clinical MS and a decline of their Kurtzke extended disability status scale ( EDSS ) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell ( HSC ) transplantation using a myeloablative conditioning regimen of cyclophosphamide ( 120 mg/kg ) , methylprednisolone ( 4 g ) and total body irradiation ( 1200 cGy ) . Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells . The average time of follow-up is 8 months ( range 6–10 months ) . Despite withdrawal of all immunosuppressive medications , functional improvements have occurred in all three patients . We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis . Stem cell transplantation has result ed in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time There were 21 patients with rapidly progressive multiple sclerosis ( MS ) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell ( HSC ) support with no 1-year mortality . Following transplantation , one patient had a confirmed acute attack of MS . Neurologic progression defined by the exp and ed disability status scale ( EDSS ) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less . In 8 of 12 patients with high pretransplantation disability scores ( EDSS > 6.0 ) , progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration . There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment . Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation ( HSCT ) are not effective for patients with progressive disease and high pretransplantation disability scores . Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity . Specifically , more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup BACKGROUND AND OBJECTIVES Autologous stem cell transplantation ( ASCT ) is currently being evaluated as a therapy for patients with multiple sclerosis ( MS ) . We report the results of a phase II trial to evaluate feasibility and toxicity of CD34 + selected ASCT ( CD34+/ASCT ) and treatment results at one year of follow-up . DESIGN AND METHODS Patients with advanced secondary progressive ( SP ) or relapsing-remitting ( RR ) MS and confirmed worsening of the extended disability status scale ( EDSS ) in the previous year despite interferon or other immunotherapies were included . Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide ( Cy ) and granulocyte colony-stimulating factor ( G-CSF ) . CD34 + selection was performed by means of an Isolex 300 or CliniMACS device . BCNU , Cy and antithymocyte globulin ( ATG ) were administered as conditioning regimen . RESULTS Fifteen patients ( 9 SPMS and 6 RRMS ) with a median EDSS of 6.0 ( 4.5 - 6.5 ) and a median of 3 ( 1 - 7 ) relapses in the previous year were included . Mobilization was unsuccessful in one patient . During mobilization , one patient had a transient neurologic deterioration . The main complication during ASCT were engraftment syndrome , which developed in three patients , CMV reactivation in one , and neurologic deterioration in two patients coinciding with high-fever related to ATG . Hematologic recovery was fast and complete in all cases . At 12 months , the EDSS had improved in three patients , worsened in two and remained stable in nine . Despite withdrawal of all immunosuppressive therapy only two patients had relapses . Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal b and s persisted in the cerebrospinal fluid of all evaluated cases . INTERPRETATION AND CONCLUSIONS CD34+/ASCT using BCNU , Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS . Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease Background During the last 15 years , high-dose chemotherapy with autologous hematopoietic stem cell transplantation ( HSCT ) has globally been performed for severe multiple sclerosis ( MS ) . Most patients have been in progressive phase with long disease duration . As a rule , treatment effect has been minor or moderate . Patients Since 2004 , we have performed HSCT in nine young patients with “ malignant ” relapsing – remitting MS . Criteria for treatment were short duration of disease ; very frequent , severe relapses ; recent improvement periods indicating potential for recovery after strong immunosuppression . Findings Median age at treatment was 27 ( range 9–34 ) years , MS duration 26 ( 4–100 ) months , and annualized relapse rate 10 ( 4–12 ) . Median Disability Status Scale ( extended disability status scale , EDSS ) at HSCT was 7.0 ( 3.5–8.0 ) . Median follow-up time April 2008 is 29 ( 23–47 ) months . Median EDSS improvement is 3.5 ( 1.0–7.0 ) , clearly surpassing most previous reports . One patient relapsed mildly with rapid recovery 7 months after HSCT . All patients are otherwise stable , median EDSS being 2.0 ( 0–6.0 ) . Before HSCT , 61 relapses occurred in 82 patient months ; during follow-up , one relapse in 289 patient months . Conclusion This small series of patients with “ malignant ” relapsing – remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course . It further suggests that future criteria for HSCT in MS should be close to the present ones IMPORTANCE No current therapy for relapsing-remitting multiple sclerosis ( MS ) results in significant reversal of disability . OBJECTIVE To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS . DESIGN , SETTING , AND PARTICIPANTS Case series of patients with relapsing-remitting MS ( n = 123 ) or secondary -progressive MS ( n = 28 ) ( mean age , 36 years ; range , 18 - 60 years ; 85 women ) treated at a single US institution between 2003 and 2014 and followed up for 5 years . Final follow-up was completed in June 2014 . INTERVENTIONS Treatment with cyclophosphamide and alemtuzumab ( 22 patients ) or cyclophosphamide and thymoglobulin ( 129 patients ) followed by infusion of unmanipulated peripheral blood stem cells . MAIN OUTCOMES AND MEASURES Primary end point was reversal or progression of disability measured by change in the Exp and ed Disability Status Scale ( EDSS ) score of 1.0 or greater ( score range , 0 - 10 ) . Secondary outcomes included changes in the Neurologic Rating Scale ( NRS ) score of 10 or greater ( score range , 0 - 100 ) , Multiple Sclerosis Functional Composite ( MSFC ) score , quality -of-life Short Form 36 question naire scores , and T2 lesion volume on brain magnetic resonance imaging scan . RESULTS Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years . Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 ( interquartile range [ IQR ] , 1.5 to 4.0 ; n = 82 ) at 2 years and to 2.5 ( IQR , 1.9 to 4.5 ; n = 36 ) at 4 years ( P < .001 at each assessment ) . There was significant improvement in disability ( decrease in EDSS score of ≥1.0 ) in 41 patients ( 50 % ; 95 % CI , 39 % to 61 % ) at 2 years and in 23 patients ( 64 % ; 95 % CI , 46 % to 79 % ) at 4 years . Four-year relapse-free survival was 80 % and progression-free survival was 87 % . The NRS scores improved significantly from a pretransplant median of 74 to 88.0 ( IQR , 77.3 to 93.0 ; n = 78 ) at 2 years and to 87.5 ( IQR , 75.0 to 93.8 ; n = 34 ) at 4 years ( P < .001 at each assessment ) . The median MSFC scores were 0.38 ( IQR , -0.01 to 0.64 ) at 2 years ( P < .001 ) and 0.45 ( 0.04 to 0.60 ) at 4 years ( P = .02 ) . Total quality -of-life scores improved from a mean of 46 ( 95 % CI , 43 to 49 ) pretransplant to 64 ( 95 % CI , 61 to 68 ) at a median follow-up of 2 years posttransplant ( n = 132 ) ( P < .001 ) . There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 ( IQR , 2.78 to 22.08 cm3 ) to 5.74 cm3 ( IQR , 1.88 to 14.45 cm3 ) ( P < .001 ) at the last posttransplant assessment ( mean follow-up , 27 months ; n = 128 ) . CONCLUSIONS AND RELEVANCE Among patients with relapsing-remitting MS , nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes . These preliminary findings from this uncontrolled study require confirmation in r and omized trials |
444 | 26,878,893 | Our systematic review of the literature and meta- analysis suggest that TCS has high diagnostic accuracy in the diagnosis of PD when compared to healthy control | A large number of articles have reported substantia nigra hyperechogenicity in Parkinson 's disease ( PD ) and have assessed the diagnostic accuracy of transcranial sonography ( TCS ) ; however , the conclusions are discrepant .
Consequently , this systematic review and meta- analysis aims to consoli date the available observational studies and provide a comprehensive evaluation of the clinical utility of TCS in PD . | Neuroimaging is known to complement clinical findings in the diagnostic work up of parkinsonian syndromes . Recently , transcranial ultrasound was reported to have a high diagnostic yield in differentiating idiopathic Parkinson ’s disease ( IPD ) from atypical parkinsonian syndromes . This report summarises the sonographic findings of 102 patients with IPD , 34 patients with multiple system atrophy , and 21 patients with progressive supranuclear palsy . Increased echogenicity of the substantia nigra is predictive for IPD whereas a low echogenic substantia nigra , particularly when combined with a hyperechogenic lentiform nucleus , strongly suggests an atypical Parkinsonian syndrome . The underlying causes for the differential echo pattern of the substantia nigra remain unknown Background Hyperechogenicity of the substantia nigra ( SN+ ) , detected by transcranial sonography ( TCS ) , was reported as a characteristic finding in Parkinson 's disease ( PD ) , with high diagnostic accuracy values , when compared mainly to healthy controls or essential tremor ( ET ) group . However , some data is accumulating that the SN + could be detected in other neurodegenerative and even in non-neurodegenerative disorders too . Our aim was to estimate the diagnostic accuracy of TCS , mainly focusing on the specificity point , when applied to a range of the parkinsonian disorders , and comparing to the degenerative cognitive syndromes . Methods A prospect i ve study was carried out at the Hospital of Lithuanian University of Health Sciences from January until September 2011 . Initially , a TCS and clinical examination were performed on 258 patients and 76 controls . The General Electric Voluson 730 Expert ultrasound system was used . There were 12.8 % of cases excluded with insufficient temporal bones , and 4.3 % excluded with an unclear diagnosis . The studied sample consisted of the groups : PD ( n = 71 , 33.2 % ) , ET ( n = 58 , 27.1 % ) , PD and ET ( n = 10 , 4.7 % ) , atypical parkinsonian syndromes ( APS ) ( n = 3 , 1.4 % ) , hereditary neurodegenerative parkinsonism ( HDP ) ( n = 3 , 1.4 % ) , secondary parkinsonism ( SP ) ( n = 23 , 10.8 % ) , mild cognitive impairment ( MCI ) ( n = 33 , 15.4 % ) , dementia ( n = 13 , 6.1 % ) , and control ( n = 71 ) . Results There were 80.3 % of PD patients at stages 1 & 2 according to Hoehn and Yahr . At the cut-off value of 0.20 cm2 of the SN+ , the sensitivity for PD was 94.3 % and the specificity - 63.3 % ( ROC analysis , AUC 0.891 ) , in comparison to the rest of the cohort . At the cut-off value of 0.26 cm2 , the sensitivity was 90 % and the specificity 82.4%.The estimations for the lowest specificity for PD , in comparison to the latter subgroups ( at the cut-off values of 0.20 cm2 and 0.26 cm2 , respectively ) were : 0 % and 33.3 % to APS , 33.3 % and 66.7 % to HDP , 34.8 % and 69.6 % to SP , 55.2 % and 82.8 % to ET , 75 % and 91.7 % to dementia . Conclusions The high sensitivity of the test could be employed as a valuable screening tool . But TCS is more useful as a supplementary diagnostic method , due to the specificity values not being comprehensive Background Essential tremor ( ET ) and Parkinson ’s disease ( PD ) are considered distinct disorders . The aim of the study was to look for a link or any distinguishing features by transcranial sonography ( TCS ) , together with the clinical examination findings in a group of patients with overlapping phenotype of ET and PD ( ET-PD ) . Methods A prospect i ve observational case-control study was carried out from the 3rd January 2011 until 30th January 2013 at the Hospital of Lithuanian University of Health Sciences . The final study group consisted of 15 patients with ET-PD , 116 patients with ET-only and 141 patients with PD-only . The control group included 101 subjects . Clinical diagnosis was of a diagnostic st and ard . Results The main ultrasonographic findings in the ET-PD group were similar to those of the PD-only : hyperechogenicity of the substantia nigra ( 66.7 % , p < 0.001 ) and nuclei raphe interruptions/absence ( 38.5 % , p < 0.001 ) . The single distinguishing TCS finding in ET-PD group was a lentiform nucleus hyperechogenicity ( 26.7 % ) , however this was only significant when compared to controls ( p = 0.006 ) . An asymmetrical onset of symptoms ( 73.3 % ) in ET-PD group was characteristic to PD-only . The ET-PD patients had the longest disease duration ( median 6 years , p < 0.001 ) , the most frequent rate of positive family history ( 53.3 % , p = 0.005 ) , rather low prevalence of cogwheel rigidity ( 26.7 % , p < 0.001 ) , and higher mean Hoehn & Yahr scores compared to PD-only ( 2.6 ± 0.8 vs. 1.8 ± 0.8 , p = 0.012 ) . Conclusions The main TCS findings of the present study in patients with overlapping ET-PD phenotype were similar to the PD-only group . The highest positive family history rate among ET-PD patients indicates a strong hereditary predisposition and needs genetic underpinnings . Some ET patients , who look like they may be developing co-morbid PD clinical ly , may have an alternative diagnosis for Parkinsonism , which could be delineated by TCS examination Background This study examines the clinical accuracy of movement disorder specialists in distinguishing tremor dominant Parkinson 's disease ( TDPD ) from other tremulous movement disorders by the use of st and ardised patient videos . Patients and methods Two movement disorder specialists were asked to distinguish TDPD from patients with atypical tremor and dystonic tremor , who had no evidence of presynaptic dopaminergic deficit ( subjects without evidence of dopaminergic deficit ( SWEDDs ) ) according to 123I-N-ω-fluoro-propyl- 2β-carbomethoxy-3β-(4-iodophenyl ) nortropane ( [ 123I ] FP-CIT ) single photon emission computed tomography ( SPECT ) , by ‘ blinded ’ video analysis in 38 patients . A diagnosis of parkinsonism was made if the step 1 criteria of the Queen Square Brain Bank criteria for Parkinson 's disease were fulfilled . The review er diagnosis was compared with the working clinical diagnosis drawn from the medical history , SPECT scan result , long term follow-up and in some cases the known response to dopaminergic medications . This comparison allowed a calculation for false positive and false negative rate of diagnosis of PD . Results High false positive ( 17.4 - 26.1 % ) and negative ( 6.7 - 20 % ) rates were found for the diagnosis of PD . The diagnostic distinction of TDPD from dystonic tremor was reduced by the presence of dystonic features in treated and untreated PD patients . Conclusion Clinical distinction of TDPD from atypical tremor , monosymptomatic rest tremor and dystonic tremor can be difficult due to the presence of parkinsonian features in tremulous SWEDD patients . The diagnosis of bradykinesia was particularly challenging . This study highlights the difficulty of differentiation of some cases of SWEDD from PD BACKGROUND In several pilot studies , transcranial brain sonography findings of substantia nigra and lenticular nucleus discriminated between idiopathic Parkinson disease ( PD ) and atypical parkinsonian disorders . OBJECTIVE To study the use of transcranial brain sonography in excluding the diagnosis of idiopathic PD in patients with sporadic parkinsonism . DESIGN AND SETTING All patients with parkinsonism admitted to our movement disorder clinic from January 1 , 2003 , through December 31 , 2005 , who fulfilled clinical diagnostic criteria for definite PD , probable parkinsonian variant of multiple-system atrophy ( MSA-P ) , or probable progressive supranuclear palsy ( PSP ) were prospect ively studied with transcranial brain sonography by an investigator blinded to clinical diagnoses . Patients Eligible patients included 138 with sporadic idiopathic PD ( 82 men and 56 women ; mean + /- SD age , 67.1 + /- 9.8 years ; mean + /- SD disease duration , 7.5 + /- 6.3 years ; mean + /- SD motor score on the Unified Parkinson Disease Rating Scale , 32.6 + /- 18.1 ) , 21 with MSA-P ( 10 men and 11 women ; mean + /- SD age , 65.4 + /- 9.5 years ; mean + /- SD duration of disease , 3.1 + /- 2.0 years ; mean + /- SD motor score , 33.5 + /- 16.1 ) , and 22 with PSP ( 13 men and 9 women ; mean + /- SD age , 71.2 + /- 5.5 years ; mean + /- SD duration of disease , 3.4 + /- 2.4 years ; mean + /- SD motor score , 46.2 + /- 18.9 ) . In 7 patients , transcranial brain sonography was not possible owing to insufficient temporal acoustic bone windows . MAIN OUTCOME MEASURES Sensitivity , specificity , and predictive value of transcranial brain sonography in indicating an atypical parkinsonian syndrome rather than idiopathic PD in patients with sporadic parkinsonism . RESULTS Normal echogenic substantia nigra indicated MSA-P rather than PD ( sensitivity , 90 % ; specificity , 98 % ; positive predictive value , 86 % ) , whereas third-ventricle dilatation of more than 10 mm in combination with lenticular nucleus hyperechogenicity indicated PSP rather than PD ( sensitivity , 84 % ; specificity , 98 % ; positive predictive value , 89 % ) . Normal echogenic substantia nigra combined with lenticular nucleus hyperechogenicity indicated MSA-P or PSP ( sensitivity , 59 % ; specificity , 100 % ; positive predictive value , 100 % ) . In parkinsonism with age at onset younger than 60 years , normal echogenic substantia nigra alone indicated MSA-P or PSP ( sensitivity , 75 % ; specificity , 100 % ; positive predictive value , 100 % ) . CONCLUSIONS Distinct transcranial brain sonography findings can exclude the diagnosis of PD in patients with sporadic parkinsonism . Sonographic discrimination of atypical parkinsonian syndromes from PD is clearer in patients with onset of parkinsonism at younger than 60 years BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects Transcanial sonography ( TCS ) is increasingly applied in the diagnosis of Parkinson 's disease ( PD ) , but investigator bias may influence the results of examination . Blinding the sonographer to the clinical diagnosis of 42 PD patients and 35 controls , we obtained a positive predictive value of 85.7 % and a negative predictive value of 82.9 % in the diagnosis of PD solely by interpreting the results of TCS , indicating that TCS is a valuable additional tool in the diagnosis of PD Article abstract -To detect morphologic abnormalities in Parkinson 's disease ( PD ) , we examined 30 patients with PD and 30 age- and sex-matched nonparkisonian controls by transcranial color-coded real-time sonography ( TCCS ) . In 12 severely affected PD patients , the echogenicity of the substantia nigra was distinctly increased . In the remaining 18 PD patients and in all controls , the substantia nigra was poorly visualized or nondetectable by TCCS . The degree of hyperechogenicity of the substania nigra closely correlated with the severity and duration of PD ( p < 0.001 ) . The increased echogenicity of the substania nigra notably results from nigral gliosis and reflects the stage of degeneration . NEUROLOGY 1995;45 : 182 - |
445 | 22,023,378 | Despite different cancer characteristics , a fairly universal picture of terminal disease included decreasing performance status , advancing age , weight loss , metastatic disease , disease recurrence , and laboratory abnormalities indicating extensive disease .
Most of the prognostic indicators found were continuous , independent risk factors for mortality .
We found little evidence that treatment improved survival at these terminal stages , with increased risk for toxicity .
CONCLUSION This systematic review summarizes prognostic factors in advanced cancer that are consistently associated with a median survival of 6 months or less .
There is little evidence that treatment prolongs survival at this stage | OBJECTIVE To report cancer presentations with a median survival of 6 months or less and the effect of treatment on survival . | AIM To assess whether the effectiveness of a combination of transarterial chemoembolization ( TACE ) and percutaneous ethanol injection ( PEI ) in the treatment of unresectable hepatocellular carcinoma ( HCC ) is superior to TACE alone a r and omized controlled trial was performed . METHODS The effect of combination therapy on long-term survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs , r and omly allocated to TACE-PEI ( 27 pts ) or TACE alone ( 25 pts ) . RESULTS The cumulative survival rate of the TACE group was 75.8 % at 6 mo , 62.9 % at 12 mo , and 18.0 % at 24 mo and of the TACE-PEI group 76.9 % , 61.5 % , and 38.7 % , respectively . Comparison of overall survival in both groups showed no statistically significant difference . Regarding the patients with HCCs Okuda stage I ( n = 26 ) , the median survival of the TACE-PEI group was significantly longer ( > 24 mo , median not yet reached in the study period ) compared to the TACE group ( 18.4 mo [ range 11.6 - 21.7 mo ] ; P = 0.04 ) . TACE-PEI reduced the relative risk for mortality to 0.4 ( 95%CI 0.15 - 0.96 ) compared to patients who received TACE alone . Median survival in patients with HCCs Okuda stage II or III was 5.0 mo in the TACE group ( 1.7 mo-not defined ) compared to 10.4 mo in the TACE-PEI group . CONCLUSION The combination TACE-PEI improved survival time compared to TACE alone . Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably Context Per capita Medicare spending varies considerably from region to region . The effect of greater Medicare spending on mortality , functional status , and satisfaction is not known . Contribution Using end-of-life care spending as an indicator of Medicare spending , the research ers categorized geographic regions into five quintiles of spending and examined costs and outcomes of care for hip fracture , colorectal cancer , and acute myocardial infa rct ion . Residents of high-spending regions received 60 % more care but did not have lower mortality rates , better functional status , or higher satisfaction . Implication s Medicare beneficiaries who live in higher Medicare spending regions do not necessarily have better health outcomes or satisfaction with health care than those in lower-spending regions . The Editors The inexorable growth of health care spending in the United States is widely believed to be due to the greater use of advanced technology of clear-cut benefit ( 1 ) . Policymakers argue ( and the public assumes ) that any constraints on growth are likely to be harmful ( 1 , 2 ) . Studies of regional variations in spending and medical practice , however , call these assumptions into question . Earlier research has indicated that the nearly twofold differences in Medicare spending observed across U.S. regions are not due to differences in the prices paid for medical services ( 3 , 4 ) or to differences in health or socioeconomic status ( 3 , 5 , 6 ) . Recent research , some of which is presented in Part 1 of our study , indicates that regional variations in average per capita Medicare spending are not due to more frequent performance of major surgery ( 7 , 8) and that regions with higher per capita spending are no more likely to provide higher- quality care , whether defined in terms of specific evidence -based services or in terms of greater access to basic health care ( 7 , 8) . The additional utilization in high-spending regions is largely devoted to discretionary services that have previously been demonstrated to be associated with the local supply of physicians and hospital re sources ( 5 , 6 ) . These include the frequency and type of evaluation and management services provided by physicians , the use of specialist consultations , the frequency of diagnostic tests and minor procedures , and the likelihood of treating patients with chronic disease in the inpatient or intensive care unit setting . Whether the specialist-oriented , more inpatient-based practice observed in high-spending regions offers important health benefits , however , is unknown . Although recent studies have found no benefit in terms of mortality ( 5 , 9 , 10 ) , they had limited ability to adjust for possible case-mix differences , inadequate individual-level clinical detail , and limited outcome measures . Our study was design ed to address these concerns . In Part 1 , we reported on the relationship between regional differences in spending and the content of care , quality of care , and access to care provided to four cohorts of Medicare beneficiaries . In this article , Part 2 , we describe associations between increased spending and mortality , functional status , and satisfaction with care . Methods Design Overview As described in greater detail in Part 1 , we carried out a cohort study in four parallel population s using a natural r and omization approach ( 11 ) . In this approach , one or more exposure variables allow assignment of patients into treatment groups ( different levels of average spending ) , as would a r and omized trial . Because some of the regional differences in Medicare spending are due to differences in illness levels ( enrollees in Louisiana are sicker than those in Colorado ) and price ( Medicare pays more for the same service in New York than in Iowa ) , we could not use Medicare spending itself as the exposure . We therefore assigned U.S. hospital referral regions ( HRRs ) , and thus the cohort members residing within them , to different exposure levels using a measure that reflects the component of regional variation in Medicare spending due to physician practice rather than regional differences in illness or pricethe End-of-Life Expenditure Index ( EOL-EI ) . Because regional differences in end-of-life spending are unrelated to underlying illness levels , it is reasonable to consider residence in HRRs with differing levels of end-of-life spending as a r and om event . The index was calculated as spending on hospital and physician services provided to a reference cohort distinct from the study cohorts : Medicare enrollees in their last 6 months of life . In the current paper , we also present several analyses with an alternative exposure measure , the Acute Care Expenditure Index ( AC-EI ) , to decrease concern about possible residual confounding . We confirmed that the exposures used to assign the HRRs achieved the goals of natural r and omization : 1 ) Study sample s assigned to different levels of the exposure [ the EOL-EI ] were similar in baseline health status , and 2 ) the actual quantity of services delivered to the individuals within the study sample s nevertheless differed substantially across exposure levels and was highly correlated with average per capita Medicare spending in the HRRs . We followed the cohorts for up to 5 years after their initial hospitalizations and compared the processes of care ( Part 1 ) and health outcomes ( Part 2 ) across HRRs assigned to different exposure levels . Study Cohorts The four study cohorts are described in detail in Part 1 . Briefly , we studied fee-for-service Medicare enrollees , ages 65 to 99 years , who were eligible for Medicare Parts A and B. The acute myocardial infa rct ion ( MI ) cohort was drawn from patients included in the Cooperative Cardiovascular Project , who had index hospitalizations between February 1994 and November 1995 . The hip fracture and colorectal cancer cohorts were identified based on an incident hospitalization between 1993 and 1995 . The general population sample included participants in the Medicare Current Beneficiary Survey ( MCBS ) who had initial interviews between 1991 and 1996 ( for the survival analysis ) or between 1992 and 1995 ( for the other analyses ) ( see Appendix , Section C ) . Each cohort member was placed in a spending group according to the EOL-EI ( as defined in detail in Part 1 ) in their HRR of residence at the time of the index hospitalization ( chronic disease cohorts ) , or initial interview ( MCBS cohort ) . Characteristics of the study cohorts were ascertained from a variety of sources , as described in detail in Part 1 , including Medicare administrative files and cl aims ( all four cohorts ) , chart review s ( acute MI cohort ) , in-person interview ( MCBS cohort ) , U.S Census data ( attributes of ZIP code of residence , such as income , for the three chronic disease cohorts ) , and American Hospital Association data ( to characterize hospitals ) . Assignment to Exposure Levels As we summarized here and described in detail in Part 1 , we used two approaches to determine cohort members ' exposure to different levels of Medicare spending in their HRR of residence . Previous research has shown that the dramatic differences in end-of-life treatment across U.S. regions are highly predictive of differences in total spending ( 8 , 12 ) but are not due to differences in case mix or patient preferences ( 13 ) . Our primary measure of exposure was the EOL-EI , which was calculated as age-sex-raceadjusted spending ( measured with st and ardized national prices ) on hospital and physician services provided to Medicare enrollees who were in their last 6 months of life in each of the 306 U.S. HRRs in mid-1994 to 1997 , excluding any members of the study cohorts ( Appendix , Section E ) We also repeated the major analyses with an alternative exposure measure , the AC-EI , which was based on differences across HRRs in risk-adjusted spending during an acute illness episode ( Appendix , Section F ) . Both measures were highly predictive of average age-sex-raceadjusted Medicare spending at the HRR level ( r = 0.81 for the EOL-EI and 0.79 for the AC-EI in the acute MI cohort ) and , as was shown in Part 1 , of the regional differences in utilization experienced by the study cohorts . For many analyses , we grouped HRRs into quintiles of increasing exposure to the expenditure indices . Statistical Analyses To assess the aggregate impact of any differences in individual attributes on average baseline risk for death across regions of increasing EOL-EI , we used logistic regression to determine each individual 's predicted 1-year risk for death as a function of his or her baseline characteristics . The models had modest to excellent predictive ability ( c-statistics were 0.61 for the colorectal cancer cohort , 0.68 for the hip fracture cohort , 0.77 for the acute MI cohort , and 0.82 for the MCBS cohort ) . We used these models to determine the average predicted risk for death across quintiles of Medicare expenditure indices . Mortality Analyses The association between the HRR-level expenditure index and survival was assessed by using Cox proportional-hazards regression models ( 14 ) , with the expenditure index measured both as a categorical variable ( in which each HRR was assigned to a quintile of Medicare spending based on the EOL-EI ) and a continuous variable ( using the value of the EOL-EI in the HRR of residence as the exposure ) . The survival models included independent variables to adjust for patient characteristics , hospital characteristics , and attributes of the HRR . Model fit was assessed by using methods for Cox model residuals to examine overall model fit , to test proportional hazards assumptions , and to identify influential observations . The main survival models underpredicted mortality in the first 6 months , possibly because of short-term complications that could not be adequately predicted with the available data ; however , the models provided excellent prediction of 1-year mortality rates for each cohort . The models are presented in Appendix Tables 6 , 7 , 8 , and 9 . To test whether the overall findings were BACKGROUND Cisplatin-based chemotherapy improves survival in advanced non-small-cell lung cancer . Using data from phase III trials of mitomycin , ifosfamide and cisplatin , this paper investigates whether the beneficial effect of chemotherapy on survival and quality of life seen overall is limited to certain patient subgroups . PATIENTS AND METHODS The survival benefit of chemotherapy was compared with st and ard treatment using hazard ratios for subgroups specified by stage , sex , age , histology and performance status ( PS ) . The effect on quality of life was investigated for three subgroups defined by performance status . RESULTS The overall unstratified hazard ratio for all 797 eligible patients shows a 16 % reduction in the risk of death with chemotherapy ( P = 0.02 ) . This benefit was seen for both locally advanced and extensive stage disease ( significantly in extensive disease ) . Subgroups defined by sex , age and histology consistently benefitted from chemotherapy . The hazard ratios for the three levels of performance status suggest that PS2 patients gain no survival benefit from chemotherapy . In contrast , these patients experienced the greatest improvement in quality of life during the first six weeks of chemotherapy . CONCLUSIONS Subgroup analysis suggests that the prolongation of life from cisplatin-based chemotherapy is confined to PS0/1 patients . Palliation is greater in PS2 patients Abstract Objective : To describe doctors ' prognostic accuracy in terminally ill patients and to evaluate the determinants of that accuracy . Design : Prospect i ve cohort study Setting : Five outpatient hospice programmes in Chicago Participants : 343 doctors provided survival estimates for 468 terminally ill patients at the time of hospice referral Main outcome measures : Patients ' estimated and actual survival . Results : Median survival was 24 days . Only 20 % ( 92/468 ) of predictions were accurate ( within 33 % of actual survival ) ; 63 % ( 295/468 ) were overoptimistic and 17 % ( 81/468 ) were overpessimistic . Overall , doctors overestimated survival by a factor of 5.3 . Few patient or doctor characteristics were associated with prognostic accuracy . Male patients were 58 % less likely to have overpessimistic predictions . Non-oncology medical specialists were 326 % more likely than general internists to make overpessimistic predictions . Doctors in the upper quartile of practice experience were the most accurate . As duration of doctor-patient relationship increased and time since last contact decreased , prognostic accuracy decreased . Conclusion : Doctors are inaccurate in their prognoses for terminally ill patients and the error is systematic ally optimistic . The inaccuracy is , in general , not restricted to certain kinds of doctors or patients . These phenomena may be adversely affecting the quality of care given to patients near the end of We conducted a retrospective analysis of 968 adults with acute myeloid leukemia ( AML ) on 5 recent Southwest Oncology Group trials to underst and how the nature of AML changes with age . Older study patients with AML presented with poorer performance status , lower white blood cell counts , and a lower percentage of marrow blasts . Multidrug resistance was found in 33 % of AMLs in patients younger than age 56 compared with 57 % in patients older than 75 . The percentage of patients with favorable cytogenetics dropped from 17 % in those younger than age 56 to 4 % in those older than 75 . In contrast , the proportion of patients with unfavorable cytogenetics increased from 35 % in those younger than age 56 to 51 % in patients older than 75 . Particularly striking were the increases in abnormalities of chromosomes 5 , 7 , and 17 among the elderly . The increased incidence of unfavorable cytogenetics contributed to their poorer outcome , and , within each cytogenetic risk group , treatment outcome deteriorated markedly with age . Finally , the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy . The distinct biology and clinical responses seen argue for age-specific assessment s when evaluating therapies for AML Pegylated liposomal doxorubicin is a new formulation with activity against epithelial ovarian carcinoma ( EOC ) . The authors sought to determine patient characteristics that may predict for response to this treatment and favorable time to failure as well as survival Summary . Death during the induction phase of chemotherapy remains a common event in patients with aggressive non‐Hodgkin 's lymphoma ( NHL ) . In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ ACVB ( doxorubicin , cyclophosphamide , vindesine , bleomycin , prednisone ) regimen ] , we determined the clinical and biological parameters that were predictive of early death . Early death was defined as death , for whatever reason , occurring within 100 d of r and omization . Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was design ed . Among the 2210 patients treated with ACVB , there were 162 ( 7·3 % ) early deaths . There was no significant reduction in the rate of early death between 1987 and 1998 . In a multivariate analysis , age > 60 years , Eastern Cooperative Oncology Group performance status > 1 , serum lactate dehydrogenase > normal , serum albumin < 30 g/l , leucocyte counts > 10 × 109/l and haemoglobin levels < 8·5 g/dl were found to be independent predictive factors for early death . An early death index was design ed , enabling the evaluation of the individual risk of early death in young ( range 2–31 % risk of early death ) and elderly patients ( range 5–53 % ) . Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death The aim of the project was to identify clinical and quality of life ( QL ) factors that together predict survival and response to chemotherapy in advanced breast cancer . Potential prognostic factors were studied in 187 women with baseline QL data from a trial of paclitaxel versus doxorubicin as first-line chemotherapy . Demographic and clinical factors studied were age , performance status , dominant site of disease and preceding disease-free interval ( DFI ) . Factors from the EORTC QLQ-C30 were all function scales , fatigue , nausea/vomiting , pain , dyspnoea , insomnia , loss of appetite and global QL . The proportional hazards regression model with stratification for treatment , and the logistic regression model adjusting for treatment arm were used for univariate and multivariate analyses of survival and response to treatment , respectively . For survival , multiple sites of visceral disease , pain , global QL and fatigue were significant prognostic factors in the univariate analysis . The final multivariate model predicted poor survival with multiple sites of visceral disease ( P=0.003 ) , DFI < /=2 years ( P=0.026 ) and pain ( P=0.003 ) . For response , age , dyspnoea , fatigue and global QL were significant predictive factors in the univariate analysis . The final multivariate model for response selected DFI ( P=0.009 ) , multiple sites of visceral disease ( P=0.037 ) and dyspnoea ( P=<0.001 ) using forward selection , but model instability was indicated by the inclusion of fatigue and emotional function in the final model when backward selection was used . In addition to known clinical factors , patient-assessed QL variables appear to be prognostic for survival and response to chemotherapy in women with advanced breast cancer . However , identification of prognostic factors from responses to question naires may be unstable , and their reliability and clinical utility should be tested prospect ively CONTEXT Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival . If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis , then treatment choices may not reflect each patient 's true values . OBJECTIVE To test the hypothesis that among terminally ill cancer patients an accurate underst and ing of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension . DESIGN Prospect i ve cohort study . SETTING Five teaching hospitals in the United States . PATIENTS A total of 917 adults hospitalized with stage III or IV non-small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Underst and Prognoses and Preferences for Outcomes and Risks of Treatments ( SUPPORT ) . MAIN OUTCOME MEASURES Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort , patient and physician estimates of the probability of 6-month survival , and actual 6-month survival . RESULTS Patients who thought they were going to live for at least 6 months were more likely ( odds ratio [ OR ] , 2.6 ; 95 % confidence interval [ CI ] , 1.8 - 3.7 ) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10 % chance that they would not live 6 months . This OR was highest ( 8.5 ; 95 % CI , 3.0 - 24.0 ) among patients who estimated their 6-month survival probability at greater than 90 % but whose physicians estimated it at 10 % or less . Patients overestimated their chances of surviving 6 months , while physicians estimated prognosis quite accurately . Patients who preferred life-extending therapy were more likely to undergo aggressive treatment , but controlling for known prognostic factors , their 6-month survival was no better . CONCLUSIONS Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies |
446 | 18,390,973 | Conclusion : No statistically significant differences in effects were found between EMG-NMES and usual care . | Objective : To assess whether EMG-triggered neuromuscular electrical stimulation ( EMG-NMES ) applied to the extensor muscles of the forearm improves h and function after stroke . | It has been proposed that somatosensory stimulation in the form of electromyographically triggered neuromuscular electrical stimulation ( NMES ) to the peripheral nerve can influence functional measures of motor performance in subjects with stroke and can additionally produce changes in cortical excitability . Using a controlled , double-blind design , we studied the effects of intensive ( 60 h/3 weeks ) treatment at home with NMES compared with a sham treatment , applied to the extensor muscles of the hemiplegic forearm to facilitate h and opening in 16 chronic stroke subjects . We investigated improvement in functional use of the h and and change in cortical activation as measured by functional magnetic resonance imaging ( fMRI ) . Following treatment , subjects improved on measures of grasp and release of objects ( Box and Block Test and Jebsen Taylor H and Function Test [ JTHFT ] : small objects , stacking , heavy cans ) , isometric finger extension strength , and self-rated Motor Activity Log ( MAL ) : Amount of Use and How Well score . The sham subjects did not improve on any grasp and release measure or self-rated scale , but did improve on isometric finger extension strength . Importantly , however , following crossover , these subjects improved further in the measure of strength , grasp and release ( Box and Block [ JTHFT ] : page turning ) , and self-rated MAL : Amount of Use score and How Well score . Using fMRI and a finger-tracking task , an index of cortical intensity in the ipsilateral somatosensory cortex increased significantly from pre-test to post-test following treatment . Cortical activation , as measured by voxel count , did not change . These findings suggest that NMES may have an important role in stimulating cortical sensory areas allowing for improved motor function BACKGROUND AND PURPOSE It has been suggested that cyclic neuromuscular electrical stimulation ( ES ) may enhance motor recovery after stroke . We have investigated the effects of ES of the wrist extensors on impairment of wrist function and on upper-limb disability in patients being rehabilitated after acute stroke . METHODS We recruited 60 hemiparetic patients ( mean age , 68 years ) 2 to 4 weeks after stroke into a r and omized , controlled , parallel-group study comparing st and ard rehabilitation treatment with st and ard treatment plus ES of wrist extensors ( 3 times 30 minutes daily for 8 weeks ) . Isometric strength of wrist extensors was measured using a device built for that purpose . Upper-limb disability was assessed with use of the Action Research Arm Test ( ARAT ) . Observations were continued for 32 weeks ( 24 weeks after the finish of ES or the control intervention phase ) . RESULTS The change in isometric strength of wrist extensors ( at an angle of 0 degrees extension ) was significantly greater in the ES group than the control group at both 8 and 32 weeks ( P=0.004 , P=0.014 by Mann Whitney U test ) . At week 8 the grasp and grip subscores of the ARAT increased significantly in the ES group compared with that in the control group ( P=0.013 and P=0.02 , respectively ) ; a similar trend was seen for the total ARAT score ( P=0.11 ) . In the subgroup of 33 patients with some residual wrist extensor strength at study entry ( moment at 0 degrees extension > 0 ) , the ARAT total score had increased at week 8 by a mean of 21.1 ( SD , 12.7 ) in the ES group compared with 10.3 ( SD , 9.0 ) in the control group ( P=0.024 , Mann Whitney U test ) ; however , at 32 weeks the differences between these 2 subgroups were no longer statistically significant . CONCLUSIONS ES of the wrist extensors enhances the recovery of isometric wrist extensor strength in hemiparetic stroke patients . Upper-limb disability was reduced after 8 weeks of ES therapy , with benefits most apparent in those with some residual motor function at the wrist . However , it is not clear how long the improvements in upper-limb disability are maintained after ES is discontinued Motor improvements in chronic stroke recovery accrue from coupled protocol s of bilateral movements and active neuromuscular stimulation . This experiment investigated coupled protocol s and within-limb transfer between distal and proximal joint combinations . The leading question focused on within-limb transfer of coupled protocol s on distal joints to a bimanual aim ing task that involved proximal joints . Twenty-six volunteers completed one of three motor recovery protocol s according to group assignments : ( 1 ) coupled bilateral involved concurrent wrist/finger movements on the unimpaired limb coupled with active stimulation on the impaired limb ; ( 2 ) unilateral/active stimulation involved neuromuscular electromyogram-triggered stimulation on the impaired wrist/fingers ; and ( 3 ) no protocol ( control group ) . During the pretest and posttest , subjects performed transverse plane target aim ing movements ( 29 cm ) with vision available . The coupled bilateral group showed positive intralimb transfer post-treatment when both arms moved simultaneously . During the posttest , the coupled bilateral group displayed improved movement time , higher peak limb velocity , less variability in peak velocity , and less percentage of total movement time in the deceleration phase than during the pretest . The evidence confirms that within-limb transfer from distal joint training to proximal joint combinations is viable and generalizable in chronic stroke rehabilitation . Moreover , these intralimb transfer findings extend the evidence favoring motor improvements for coupled bilateral protocol s during chronic stroke CONTEXT Single-site studies suggest that a 2-week program of constraint-induced movement therapy ( CIMT ) for patients more than 1 year after stroke who maintain some h and and wrist movement can improve upper extremity function that persists for at least 1 year . OBJECTIVE To compare the effects of a 2-week multisite program of CIMT vs usual and customary care on improvement in upper extremity function among patients who had a first stroke within the previous 3 to 9 months . DESIGN AND SETTING The Extremity Constraint Induced Therapy Evaluation ( EXCITE ) trial , a prospect i ve , single-blind , r and omized , multisite clinical trial conducted at 7 US academic institutions between January 2001 and January 2003 . PARTICIPANTS Two hundred twenty-two individuals with predominantly ischemic stroke . INTERVENTIONS Participants were assigned to receive either CIMT ( n = 106 ; wearing a restraining mitt on the less-affected h and while engaging in repetitive task practice and behavioral shaping with the hemiplegic h and ) or usual and customary care ( n = 116 ; ranging from no treatment after concluding formal rehabilitation to pharmacologic or physiotherapeutic interventions ) ; patients were stratified by sex , prestroke dominant side , side of stroke , and level of paretic arm function . MAIN OUTCOME MEASURES The Wolf Motor Function Test ( WMFT ) , a measure of laboratory time and strength-based ability and quality of movement ( functional ability ) , and the Motor Activity Log ( MAL ) , a measure of how well and how often 30 common daily activities are performed . RESULTS From baseline to 12 months , the CIMT group showed greater improvements than the control group in both the WMFT Performance Time ( decrease in mean time from 19.3 seconds to 9.3 seconds [ 52 % reduction ] vs from 24.0 seconds to 17.7 seconds [ 26 % reduction ] ; between-group difference , 34 % [ 95 % confidence interval { CI } , 12%-51 % ] ; P<.001 ) and in the MAL Amount of Use ( on a 0 - 5 scale , increase from 1.21 to 2.13 vs from 1.15 to 1.65 ; between-group difference , 0.43 [ 95 % CI , 0.05 - 0.80 ] ; P<.001 ) and MAL Quality of Movement ( on a 0 - 5 scale , increase from 1.26 to 2.23 vs 1.18 to 1.66 ; between-group difference , 0.48 [ 95 % CI , 0.13 - 0.84 ] ; P<.001 ) . The CIMT group achieved a decrease of 19.5 in self-perceived h and function difficulty ( Stroke Impact Scale h and domain ) vs a decrease of 10.1 for the control group ( between-group difference , 9.42 [ 95 % CI , 0.27 - 18.57 ] ; P=.05 ) . CONCLUSION Among patients who had a stroke within the previous 3 to 9 months , CIMT produced statistically significant and clinical ly relevant improvements in arm motor function that persisted for at least 1 year . Trial Registration clinical trials.gov Identifier : NCT00057018 Background and Purpose — Constraint-induced movement therapy ( CIMT ) is a rehabilitative strategy used primarily with the post-stroke population to increase the functional use of the neurologically weaker upper extremity through massed practice while restraining the lesser involved upper extremity . Whereas research evidence supports CIMT , limited evidence exists regarding the characteristics of individuals who benefit most from this intervention . The goal of this study was to investigate the potential of 5 measures to predict functional CIMT outcomes . Methods — A convenience sample of 55 individuals , > 6 months after stroke , was recruited that met specific inclusion /exclusion criteria allowing for individuals whose upper extremity was mildly to severely involved . They participated in CIMT 6 hours per day . Pretest , post-test , and follow-up assessment s were performed to assess the outcomes for the Wolf Motor Function Test ( WMFT ) . The potential predictors were minimal motor criteria ( active extension of the wrist and 3 fingers ) , active finger extension/grasp release , grip strength , Fugl – Meyer upper extremity motor score , and the Frenchay score . A step-wise regression analysis was used in which the potential predictors were entered in a linear regression model with simultaneous entry of the dependent variables ’ pretest score as the covariate . Two regressions models were determined for the dependent variable , for immediate post-test , and for follow-up post-test . Results — Finger extension was the only significant predictor of WMFT outcomes . Conclusions — When using finger extension/grasp release as a predictor in the regression equations , one can predict individual ’s follow-up scores for CIMT . This experiment provides the most comprehensive investigation of predictors of CIMT outcomes to date Background and Purpose — To compare a computerized arm trainer ( AT ) , allowing repetitive practice of passive and active bilateral forearm and wrist movement cycle , and electromyography-initiated electrical stimulation ( ES ) of the paretic wrist extensor in severely affected subacute stroke patients . Method — A total of 44 patients , 4 to 8 weeks after stroke causing severe arm paresis ( Fugl – Meyer Motor Score [ FM , 0 to 66 ] < 18 ) , were r and omly assigned to either AT or ES . All patients practice d 20 minutes every workday for 6 weeks . AT patients performed 800 repetitions per session with the robot and ES patients performed 60 to 80 wrist extensions per session . The primary outcome measure was the blindly assessed FM ( 0 to 66 ) , and the secondary measures were the upper limb muscle power ( Medical Research Council [ MRC ] sum , 0 to 45 ) and muscle tone ( Ashworth score sum , 0 to 25 ) , assessed at the beginning and end of treatment and at 3-month follow-up . Results — The AT group had a higher Barthel Index score at baseline , but the groups were otherwise homogenous . As expected , FM and MRC sum scores improved overtime in both groups but significantly more in the robot AT group . The initial Barthel Index score had no influence . In the robot AT group , FM score was 15 points higher at study end and 13 points higher at 3-month follow-up than the control ES group . MRC sum score was 15 points higher at study end and at 3-month follow-up compared with the control ES group . Muscle tone remained unchanged , and no side effects occurred . Conclusion — The computerized active arm training produced a superior improvement in upper limb motor control and power compared with ES in severely affected stroke patients . This is probably attributable to the greater number of repetitions and the bilateral approach Positional feedback ( PF ) and electrical stimulation were combined in a new treatment modality for facilitating wrist extension in stroke patients . Thirty adult hemiparetic patients lacking normal voluntary wrist extension were r and omly placed in control and study groups . The control group received conventional therapy while the study group received positional feedback stimulation training ( PFST ) in addition to conventional treatment . At the end of the 4-week program , study patients showed a 280 % increase in isometric extension torque when the wrist was positioned in 30 degrees of extension and 70 % increase when positioned in 30 degrees of flexion . Control patients showed no significant changes in torque . Study patients made an average 200 % gain in selective range of motion over their starting levels while controls made only a 50 % increase . Treatment using automated PFST equipment allows controlled repetitive isotonic exercise and facilitation of wrist extension without continuous one-on-one therapist/patient supervision Background and Purpose — Overcoming chronic hemiparesis from a cerebrovascular accident ( CVA ) can be challenging for many patients , especially after the first 12 months after the CVA . With the use of established motor control theories , the present study investigated electromyogram (EMG)-triggered neuromuscular stimulation and bilateral coordination training . Methods — Twenty-five CVA subjects volunteered to participate in this motor recovery protocol study . Subjects were r and omly assigned to 1 of 3 groups : ( 1 ) coupled protocol of EMG-triggered stimulation and bilateral movement ( n=10 ) ; ( 2 ) EMG-triggered stimulation and unilateral movement ( n=10 ) ; or ( 3 ) control ( n=5 ) . All participants completed 6 hours of rehabilitation during a 2-week period according to group assignments . Motor capabilities of the wrist and fingers were evaluated on the basis of 3 categories of motor tasks in a pretest-posttest control group design . Results — Significant findings for the ( 1 ) number of blocks moved in a functional task , ( 2 ) chronometric reaction times to initiate movements , and ( 3 ) sustained muscle contraction capability all favored the coupled bilateral movement training and EMG-triggered neuromuscular stimulation protocol group . In addition , the unilateral movement/stimulation group exceeded the control group in the number of blocks moved and rapid onset of muscle contractions . Conclusions — This new evidence is convincing in that subjects in the coupled protocol group were able to demonstrate enhanced voluntary motor control across 3 categories of tasks . Chronic hemiparesis decreased considerably in the wrist and fingers as CVA patients exp and ed their motor repertoire BACKGROUND AND PURPOSE After stroke , many individuals have chronic unilateral motor dysfunction in the upper extremity that severely limits their functional movement control . The purpose of this study was to determine the effect of electromyography-triggered neuromuscular electrical stimulation on the wrist and finger extension muscles in individuals who had a stroke > or = 1 year earlier . METHODS Eleven individuals volunteered to participate and were r and omly assigned to either the electromyography-triggered neuromuscular stimulation experimental group ( 7 subjects ) or the control group ( 4 subjects ) . After completing a pretest involving 5 motor capability tests , the poststroke subjects completed 12 treatment sessions ( 30 minutes each ) according to group assignments . Once the control subjects completed 12 sessions attempting wrist and finger extension without any external assistance and were posttested , they were then given 12 sessions of the rehabilitation treatment . RESULTS The Box and Block test and the force-generation task ( sustained muscular contraction ) revealed significant findings ( P<0 . 05 ) . The experimental group moved significantly more blocks and displayed a higher isometric force impulse after the rehabilitation treatment . CONCLUSIONS Two lines of evidence clearly support the use of the electromyography-triggered neuromuscular electrical stimulation treatment to rehabilitate wrist and finger extension movements of hemiparetic individuals > or = 1 year after stroke . The treatment program decreased motor dysfunction and improved the motor capabilities in this group of poststroke individuals Active neuromuscular stimulation is an effective behavioral intervention for motor recovery improvements after a stroke . However , the most effective active neuromuscular stimulation duration s have not been determined . The present experiment investigated active stimulation duration s ( 0 , 5 , and 10 s ) coupled with bilateral movements on progress toward motor recovery in wrist and finger extension . Twenty-six stroke survivors with chronic hemiparesis were r and omly assigned to the stimulation duration groups , and subjects completed 4 days of rehabilitation training over a 2-week period . Mixed design analyses of variance on the Box and Block scores , chronometric reaction times , and force modulation of the sustained muscle contraction task revealed distinct motor recovery improvements for both the 5 and 10 s stimulation duration groups in comparison to the 0 s duration control group . Further , the number of blocks moved by the 10-s duration group exceeded those moved by the 5-s duration group . In conclusion , the 5 and 10 s duration active stimulation/bilateral movement groups decreased residual motor dysfunctions that persisted beyond 12 months post stroke BACKGROUND AND PURPOSE To improve the accuracy of early postonset prediction of motor recovery in the flaccid hemiplegic arm , the effects of change in motor function over time on the accuracy of prediction were evaluated , and a prediction model for the probability of regaining dexterity at 6 months was developed . METHODS In 102 stroke patients , dexterity and paresis were measured with the Action Research Arm Test , Motricity Index , and Fugl-Meyer motor evaluation . For model development , 23 c and i date determinants were selected . Logistic regression analysis was used for prognostic factors and model development . RESULTS At 6 months , some dexterity in the paretic arm was found in 38 % , and complete functional recovery was seen in 11.6 % of the patients . Total anterior circulation infa rcts , right hemisphere strokes , homonymous hemianopia , visual gaze deficit , visual inattention , and paresis were statistically significant related to a poor arm function . Motricity Index leg scores of at least 25 points in the first week and Fugl-Meyer arm scores of 11 points in the second week increasing to 19 points in the fourth week raised the probability of developing some dexterity ( Action Research Arm Test > or=10 points ) from 74 % ( positive predictive value [ PPV ] , 0.74 ; 95 % confidence interval [ CI ] , 0.63 to 0.86 ) to 94 % ( PPV , 0.83 ; 95 % CI , 0.76 to 0.91 ) at 6 months . No change in probabilities of prediction dexterity was found after 4 weeks . CONCLUSIONS Based on the Fugl-Meyer scores of the flaccid arm , optimal prediction of arm function outcome at 6 months can be made within 4 weeks after onset . Lack of voluntary motor control of the leg in the first week with no emergence of arm synergies at 4 weeks is associated with poor outcome at 6 months We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 Objective : To investigate the effects of movement imagery-assisted electromyography (EMG)-triggered feedback ( focused on paretic wrist dorsiflexors ) on the arm — h and function of stroke patients . Design : Single-blinded , longitudinal , multicentre r and omized controlled trial . Measurements were performed ( on average ) 54 days post stroke ( baseline ) , three months later ( post training ) and at 12 months post baseline . Setting : Two rehabilitation centres . Subjects : Twenty-seven patients with a first-ever , ischaemic , subacute stroke . Interventions : A reference group received conventional electrostimulation , while the experimental group received arm — h and function training based on EMG-triggered feedback combined with movement imagery . Both groups were trained for three months , 5 days/week , 30 minutes/day , in addition to their therapy as usual . Main measures : Arm — h and function was evaluated using the upper extremity-related part of the Brunnstrom Fugl-Meyer test and the Action Research Arm test . Results : During training , Brunnstrom Fugl-Meyer scores improved 8.7 points and Action Research Arm scores by 19.4 points ( P < 0.0001 ) in both groups relative to baseline results , rising to 13.3 and 28.4 points respectively at one year follow-up ( P < 0.0001 ) . No between-group differences were found at any time . Conclusions : EMG-triggered feedback stimulation did not lead to more arm — h and function improvement relative to conventional electrostimulation . However , in contrast to many clinical reports , a significant improvement was still observed in both groups nine months after treatment ceased OBJECTIVE To assess the efficacy of electromyogram (EMG)-triggered neuromuscular stimulation ( EMG-stim ) in enhancing upper extremity motor and functional recovery of acute stroke survivors . DESIGN A pilot r and omized , single-blinded clinical trial . SETTING Freest and ing inpatient rehabilitation facility . PATIENTS Nine subjects who were within 6 weeks of their first unifocal , nonhemorrhagic stroke were r and omly assigned to either the EMG-stim ( n = 4 ) or control ( n = 5 ) group . All subjects had a detectable EMG signal ( > 5 microV ) from the surface of the paretic extensor carpi radialis and voluntary wrist extension in synergy or in isolation with muscle grade of < 3/5 . INTERVENTION All subjects received two 30-minute sessions per day of wrist strengthening exercises with EMG-stim ( experimental ) or without ( control ) for the duration of their rehabilitation stay . MAIN OUTCOME MEASURES Upper extremity Fugl-Meyer motor assessment and the feeding , grooming , and upper body dressing items of the Functional Independence Measure ( FIM ) were assessed at study entry and at discharge . RESULTS Subjects treated with EMG-stim exhibited significantly greater gains in Fugl-Meyer ( 27.0 vs 10.4 ; p = .05 ) , and FIM ( 6.0 vs 3.4 ; p = .02 ) scores compared with controls . CONCLUSION Data suggest that EMG-stim enhances the arm function of acute stroke survivors 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 . Objectives : ( 1 ) To determine the feasibility of a home-based electromyography triggered neuromuscular stimulation ( ETMS ) programme ; and ( 2 ) to determine ETMS efficacy in increasing affected wrist extension and reducing affected arm impairment . Design : R and omized , controlled , pre-lpost , cross-over design . Setting : Outpatient rehabilitation hospital . Patients : Twelve chronic stroke patients with palpable muscle contraction in their affected wrist extensors but no movement ( 7 males ; mean age=59.75 years , age range 44 - 75 years ; mean time since stroke=52.75 months , range 13 - 131 months ) . Intervention : Subjects were r and omly assigned to receive either : ( a ) ETMS use twice every weekday in 35-min increments during an eight-week period followed by an eight-week home exercise programme ( ETMS/home exercise programme ) ( n=8 ) ; or ( b ) an eight-week home exercise programme followed by use of ETMS twice every weekday in 35-min increments during an eight-week period ( home exercise programme ) ( n=4 ) . Main outcome measures : The Fugl-Meyer , Action Research Arm Test and goniometry . Results : After home exercise programme participation , subjects showed nominal or no changes on any of the outcome measures . After ETMS , patients showed modest impairment reductions , as shown by the Fugl-Meyer , and no Action Research Arm Test changes . However , both groups showed a 218 increase in active affected wrist extension after ETMS use . Conclusion : ETMS use is feasible in the home environment . Neither participation in a traditional home exercise programme nor ETMS use conveyed changes on the Fugl-Meyer or Action Research Arm Test . However , ETMS use increased active affected limb extension . This new movement may provide a potential pathway for subjects to participate in other interventions , such as modified constraint induced therapy Objective : To study the effects of electrical stimulation ( ES ) on flexion contractures in the hemiplegic wrist . Design : The investigation was carried out following an OFF ( two weeks with rehabilitation only ) - ON ( two weeks with ES treatment and rehabilitation ) - OFF ( two weeks rehabilitation only ) fixed protocol . Setting : A stroke ward and an outpatient stroke service . Subjects : Eleven hemiplegic subjects with reduced range of extension and increased resistance to passive movement at the wrist . Main measure : Quantitative measures of the hemiplegic posture at the wrist , passive range of extension and resistance to passive extension of the wrist . Measurements were taken at the start of the study and then at two-weekly intervals . Two extra measurements were taken at the end of the ON period . Results : Following two weeks treatment with ES the posture of the wrist improved and the passive range of extension increased . However , there were no significant changes in the resistance to passive movement . These benefits appeared largely to be lost two weeks after ES was discontinued . Conclusions : Short-term ES gives temporary improvements in contractures at the wrist in poststroke hemiplegia This paper describes PEDro , the Physiotherapy Evidence Data base . PEDro is a web-based data base of r and omized controlled trials and systematic review s in physiotherapy . It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro . The data base contains bibliographic details and abstract s of most English- language r and omized trials and systematic review s in physiotherapy , and of many trials and review s in other language s. Trials on the data base are rated on the basis of their method ological quality so that users of the data base can quickly identify trials of high quality . Trials and systematic review s are extensively indexed to facilitate search ing . PEDro provides an important information re source to support evidence -based clinical practice It has been proposed that somatosensory input in the form of peripheral nerve stimulation can influence functional measures of motor performance . We studied the effects of median nerve stimulation on pinch muscle strength ( a function mediated predominantly by median nerve innervated muscles ) in the affected h and of chronic stroke patients . A 2‐hour period of median nerve stimulation elicited an increase in pinch strength that outlasted the stimulation period . The improvement in muscle strength correlated with stimulus intensity and was identified in the absence of motor training . These results suggest that somatosensory stimulation may be a promising adjuvant to rehabilitation of the motor deficits in stroke patients |
447 | 20,404,262 | Moderate- quality evidence indicated that 12 to 15 g of lactose ( approximately 1 cup of milk ) is well tolerated by most adults .
Evidence was insufficient that lactose-reduced solution or milk with a lactose content of 0 to 2 g , compared with greater than 12 g , is effective in reducing symptoms of lactose intolerance .
Most individuals with presumed lactose intolerance or malabsorption can tolerate 12 to 15 g of lactose . | BACKGROUND Lactose intolerance result ing in gastrointestinal symptoms is a common health concern .
Diagnosis and management of this condition remain unclear .
PURPOSE To assess the maximum tolerable dose of lactose and interventions for reducing symptoms of lactose intolerance among persons with lactose intolerance and malabsorption . | Summary The effectiveness of a new beta-D-galactosidase pellet formation in the treatment of lactose intolerance was studied . The encapsuled beta-D-galactosidase ( lactase ) pellets were first tested in vitro for their enzymatic activity within an environment simulating gastric conditions and subsequently within an environment simulating duodenal conditions . Effectiveness was measured by the % of glucose formed by hydrolysis of lactose . The pellets were found to retain their enzymatic activity in gastric pH conditions ( mean 69±1mg/dl glucose ) and were found to hydrolyse lactose in human duodenal fluid ( 106.35±1 mg/dl).Finally the effectiveness of the new lactase formation on glucose absorption was studied in 8 lactose intolerant subjects in a r and omized , double blind , crossover trial . After fasting , the subjects were given one capsule containing 100 u/ml beta-galactosidase ( i.e. 10 pellets of 10 u/ml each ) or one capsule containing placebo pellets , followed by 100 g lactose dissolved in water . The washout period between lactose challenges was one week . Plasma glucose concentrations were measured before and at intervals after the challenges and the subjects completed symptom question naires every eight hours for 24 hours . Results showed a statistically significant in plasma glucose levels 30 , 60 , 90 and 120 min after lactose ingestion ( repeated measures analysis of variance , p<0.01 ) . Subjective ratings of the severity of abdominal cramping , belching , flatulence , vomiting and diarrhoea were significantly decreased following ingestion of the lactase pellets and lactose ( no incidence of diarrhoea ) compared with after ingestion of placebo and lactose . The results of the study were considered to be very promising as the beta-D-galactosidase formulation ( which was produced at very low cost and with great ease ) resisted inactivation in the stomach , effectively transformed lactose to glucose in vivo and reduced symptoms of lactose intolerance OBJECTIVE To evaluate the efficacy of the addition to milk , 5 min and 10 h before its consumption , of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance . DESIGN Double-blind , placebo-controlled , crossover study . SETTING University Hospital . SUBJECTS In total , 11 male and 19 female ( aged from 18 to 65 y , mean age 43.3 y ) lactose malabsorbers with intolerance participated . INTERVENTIONS Each patient underwent three H(2 ) breath tests , in a r and om order . We used 400 ml of cow 's semiskimmed milk as substrate and a beta-galactosidase obtained from K. lactis . The test A was carried out adding to the milk the enzyme ( 3000 UI ) , 10 h before its consumption ; the test B was performed adding the beta-galactosidase ( 6000 UI ) 5 min before milk ingestion and the test C was made using placebo . We evaluated the maximum breath H(2 ) concentration , the cumulative H(2 ) excretion and a clinical score based on intolerance symptoms ( bloating , abdominal pain , flatulence and diarrhoea ) . RESULTS Our study showed a significant reduction of the mean maximum H(2 ) concentration after both test A ( 12.07 + /- 7.8 p.p.m . ) and test B ( 13.97 + /- 7.99 p.p.m . ) compared with test C ( 51.46 + /- 16.12 p.p.m . ) ( ANOVA F = 54.33 , P < 0.001 ) . Similarly , there was a significant reduction of the mean cumulative H(2 ) excretion after both test A ( 1428 + /- 1156 p.p.m . ) and test B ( 1761 + /- 966 p.p.m . ) compared with test C ( 5795 + /- 2707 p.p.m . ) ( ANOVA F = 31.46 , P < 0.001 ) . We also observed a significant reduction of the mean clinical score after both test A ( 0.36 + /- 0.55 ) and test B ( 0.96 + /- 0.85 ) compared with test C ( 3.7 + /- 0.79 ) ( ANOVA F = 106.81 , P < 0.001 ) . Moreover , with regard to the mean clinical score , there was a significant reduction after test A with respect to test B ( Bonferroni 's P = 0.03 ) . CONCLUSIONS Our study shows that in lactose malabsorbers with intolerance , the lactase obtained from K. lactis can represent a valid therapeutic strategy , with objective and subjective efficacy and without side effects Low-lactose milk was produced by incubating cow 's milk with yeast lactase . Sixteen lactose tolerant and 15 intolerant volunteers ingested 500 ml of the product twice daily for 1 month . During the testing period all subjects received on three occasions the same volume of unmodified milk in double-blind tests . Symptoms recorded throughout the study and for an additional 15 day base-line observation period were : diarrhea , abdominal pain and distention , flatulence , heartburn , and headache . Low-lactose milk acceptance was excellent . No significant differences were found between tolerants and intolerants during the base-line period and while ingesting low-lactose milk . By contrast , unmodified milk induced severe symptoms only in the intolerants . Availability of low-lactose milk and of its by-products allows consumption of greater volumes of this highly nutritious food by subjects with lactose intolerance with none or less symptoms compared to unmodified milk Acidophilus milk has been reported to help patients with irritable bowel syndrome by correcting the " imbalance of flora " and to be tolerated better by lactase-deficient subjects by providing bacterial lactase in the small intestine . In a double-blind r and omized study , 61 lactase-sufficient patients with irritable bowel syndrome each ingested 240 ml of milk three times a day for 2 wk and the same amount of acidophilus milk for an additional 2 wk . The degree of symptoms during the two milk-drinking periods was the same as during the control periods . Also , 18 lactase-deficient patients ingested unaltered milk for 1 wk and acidophilus milk for 1 additional wk . There was no difference in the degree of tolerance to the two varieties of milk . In summary , patients with irritable bowel syndrome were not helped by the ingestion of acidophilus milk , and lactase-deficient patients were as intolerant to acidophilus milk as to unaltered milk We conducted blinded , controlled crossover studies to determine the effect of daily lactose feeding on colonic adaptation and intolerance symptoms . The initial study with nine lactose maldigesters showed a threefold increase in fecal beta-galactosidase activity after 16 d of lactose feeding . To determine the effects of this adaptation on breath hydrogen and intolerance symptoms , 20 lactose-maldigesting adults were r and omly assigned to lactose or dextrose supplementation for 10 d ( days 1 - 10 ) , crossing over to the other period for days 12 - 21 . The sugar dosage was increased from 0.6 to 1.0 g.kg-1.d-1 , subdivided into three equal doses , by adjusting the dose every other day . Symptoms during lactose supplementation and comparison of symptoms during the lactose and dextrose feeding periods showed no significant differences . On days 11 and 22 , challenge doses of lactose ( 0.35 g/kg ) were administered after an overnight fast , and breath hydrogen and intolerance symptoms ( abdominal pain , flatulence , and diarrhea ) were carefully monitored for 8 h. Frequency of flatus passage and flatus severity ratings after the lactose challenge decreased 50 % when studied at the end of the lactose period compared with the dextrose period . The sum of hourly breath-hydrogen concentrations ( 1 - 8 h ) was significantly reduced after the lactose feeding period ( 9 + /- 38 ppm.h ) compared with after the dextrose period ( 385 + /- 52 ppm.h , P < 0.001 ) . We conclude that there is colonic adaptation to regular lactose ingestion and this adaptation reduces lactose intolerance symptoms The possible usefulness of low-lactose milk for those lactose-intolerant subjects who develop symptoms from milk consumption was investigated . In the first part of the study , 16 intolerant subjects ( blood glucose rise less than 25 mg/100 ml ) received low-lactose skim milk containing 15 g lactose ( 2.5 cups ) and 7.5 g lactose ( 2.5 cups ) , regular skim milk containing 30 g lactose ( 2.5 cups ) , and all three milks plus a small breakfast . The low lactose milks produced significantly fewer symptoms . The food given with the milk had no significant effect on symptomatic response . The second group of 17 subjects received 25 g lactose in water ( 250 ml ) , skim milk ( 500 ml ) and whole milk ( 500 ml ) ; 10 g lactose in lactose-reduced skim ( 500 ml ) and whole milk ( 500 ml ) and whole milk ( 500 ml ) ; and a placebo ( 250 ml ) . There was a significant positive relationship between amount of lactose consumed and symptom response . The form in which the lactose was administered ( e.g. , whole versus skim milk ) was not significantly related to symptoms . It is concluded that in a symptomatic subjects a significantly greater quantity of low-lactose milk than regular milks can be consumed The use of fermented dairy foods is common in areas of the world where lactase deficiency is prevalent . Recently , we have shown that the digestion of lactose from yogurt is enhanced as compared to that from milk . This enhanced digestion is apparently due to inherent B-galactosidase in yogurt which is active in the gastrointestinal tract after consumption of the yogurt . Furthermore , yogurt is well tolerated by lactase-deficient subjects result ing in little or no gastrointestinal distress . Since other fermented and microbial-containing dairy foods are consumed worldwide and may also contain some " lactase " activity , we chose to evaluate the digestion of lactose from three of these products : pasteurized yogurt , cultured milk ( buttermilk ) , and sweet acidophilus milk . Breath hydrogen techniques were used to evaluate lactose malabsorption in nine lactase-deficient subjects . The studies demonstrated that yogurt is unique among the products tested in enhancing the digestion of lactose . Furthermore , pasteurization of yogurt eliminated the enhanced digestion of lactose , reduced the inherent lactase activity of the yogurt by 10-fold and reduced cell counts by 100-fold . Interestingly , eight of nine subjects fed cultured milk experienced gastrointestinal distress , whereas all subjects fed pasteurized yogurt were symptom free , even though the amount of malabsorbed lactose was similar The relative effectiveness of five milk products with various levels of lactose reduction [ 0 % , 50 % , 80 % ( # 1 ) , 80 % ( # 2 ) , and 95 % ] was evaluated in six subjects with lactose malabsorption . Breath hydrogen was measured for 4 h after consumption of 300 mL of each product in a single-blind , r and omized design . The mean + /- SEM maximum breath-hydrogen rise ( ppm ) after the 0 % , 50 % , 80 % ( # 1 ) , 80 % ( # 2 ) , and 95 % lactose-reduced ( LR ) milks was 31 + /- 6 , 7 + /- 3 , 5 + /- 3 , 5 + /- 2 , and 8 + /- 3 , respectively . The difference between whole milk and the LR milks was statistically significant ( P less than 0.05 ) but there was no difference between any of the LR milks . Whole milk provoked symptoms in most subjects whereas 95 % LR milk produced none . Only one of six subjects reacted to the 50 % and 80 % LR milks . The results suggest that a 50 % level of lactose reduction in milk may be adequate to relieve the signs and symptoms of milk intolerance in the majority of healthy adults with lactose malabsorption Lactose digestion from and tolerance to flavored and frozen yogurts , ice cream , and ice milk were evaluated ( 20 g lactose/meal ) in lactase-deficient subjects by use of breath hydrogen techniques . Unflavored yogurt caused significantly less hydrogen production than milk ( 37 vs 185 delta ppm X h , n = 9 ) . Flavored yogurt was intermediate ( 77 delta ppm X h ) . Subjects were free of symptoms after consuming flavored and unflavored yogurts . Of seven commercial yogurts tested , all contained significant levels of microbial beta-galactosidase ( beta-gal ) . In addition , eight subjects were fed meals of milk , ice milk , ice cream , and frozen yogurts with and without cultures containing high levels of beta-gal . Peak hydrogen excretion after consumption of frozen yogurt with high beta-gal was less than one-half of that observed after the other five test meals and intolerance symptoms were absent . Tolerance to frozen yogurt , produced under usual commercial procedures , was found to be similar to that of ice milk and ice cream In this study we examined whether small doses of lactose induced symptoms in 39 lactose maldigesters and 15 lactose digesters in a r and omized , crossover , double-blind design . The test doses were 200 mL fat-free , lactose-free milk to which 0 , 0.5 , 1.5 , and 7 g lactose was added . Every third day of a lactose-free diet , after an overnight fast , the subjects drank one of the test milks in r and om order and registered the occurrence and severity of gastrointestinal symptoms in the next 12 h. During the study , the maldigesters reported significantly more abdominal bloating ( P = 0.0003 ) and abdominal pain ( P = 0.006 ) than the digesters . There was no difference in the mean severity of the reported symptoms between the test milks and the lactose-free milk in the group of lactose maldigesters , of whom one-third did not experience any symptoms from any of the test doses . The same proportion ( 64 % ) of the maldigesters experienced symptoms after both the lactose-free milk and the milk with 7 g lactose . However , the symptoms occurred inconsistently with the different test doses in 59 % of the maldigesters . Thus , it can be concluded that the gastrointestinal symptoms in most lactose maldigesters are not induced by lactose when small amounts ( 0.5 - 7.0 g ) of lactose are included in the diet BACKGROUND A National Institutes of Health consensus conference concluded that a daily calcium intake of 1500 mg reduces the severity of osteoporosis . Because dairy products are the main natural source of dietary calcium , a diet providing 1500 mg Ca must contain large quantities of dairy products . However , it is widely believed that the lactose content of these products will not be tolerated by persons with lactose maldigestion ( approximately 30 % of the adult US population ) . OBJECTIVE We evaluated the symptoms of lactose maldigestion and digestion when the diet was supplemented with dairy products providing 1300 mg Ca/d . DESIGN Sixty-two women ( 31 with lactose maldigestion and 31 without ) were studied in a double-blind , r and omized protocol . Symptoms were compared during 1-wk periods when the diet was supplemented with 480 mL ( 2 cups ) milk , 56 g cheese , and 240 mL yogurt provided as conventional products ( 34 g lactose/d ) or as lactose-hydrolyzed products ( 2 g lactose/d ) . RESULTS Women who digested lactose reported no significant difference in symptoms between the 2 treatment periods . Women with lactose maldigestion reported significantly increased flatus frequency and subjective impression of rectal gas during the period of high lactose intake ; however , bloating , abdominal pain , diarrhea , and the global perception of overall symptom severity were not significantly different between the 2 treatment periods . CONCLUSION The symptoms result ing from lactose maldigestion are not a major impediment to the ingestion of a dairy-rich diet supplying approximately 1500 mg Ca/d A low-lactose milk was evaluated for taste acceptance and clinical symptomatology by means of a double-blind control study in two groups of individuals . One group consisted of nine milk intolerant individuals , while the other consisted of five milk tolerant individuals . Each week for 9 wk the participants were given a coded sample of skim milk , lactose hydrolyzed milk , skim milk plus glucose , or sweet acidophilus milk . Each participant was asked to consume four liters of milk during a week and keep a daily log of symptoms ( pain , bloating , nausea , flatus , emesis , bowel frequency ) along with taste acceptability . After assigning a numerical value to the intensity of symptomatology a X2 analysis was performed on the data . In the milk intolerant population lactose hydrolyzed milk produced significantly milder ( p < 0.05 ) pain and gas symptoms than the nonhydrolyzed milks . Bowel frequency was not altered between the types of milk in both groups . The lactose hydrolyzed milk did not reduce the symptoms of lactose intolerance in the milk intolerance population to the response of the control group . Although both study population s found decreased taste acceptability to the lactose hydrolyzed milk , a taste panel assessment did not show any significant differences in the milks Lactose digestion and tolerance were evaluated in 164 African Americans ranging in age from 12 to 40 y who cl aim ed intolerance to one cup ( 240 mL ) or less of milk . With use of a breath-hydrogen test with 25 g lactose as test dose and the presence or absence of symptoms , 50 % of the subjects were classified as lactose maldigesters and intolerant , 8 % were maldigesters but tolerant , 15 % were digesters but intolerant , and 27 % were digesters and tolerant . Forty-five subjects from the lactose maldigesting and intolerant group were further tested for milk intolerance in a double-blind study . Sixty-seven percent of the subjects reacted appropriately to the presence or absence of lactose in ingested milk whereas 33 % reported symptoms to both low-lactose milk and milk containing lactose . The results suggest that the cause of milk intolerance in as many as one-third of African Americans cl aim ing symptoms after ingestion of a moderate amount of milk can not be its lactose content Lactase-deficient subjects absorb lactose in yogurt more effectively than lactose in other dairy products . However , as all previous studies were performed without a double-blind design and only after a single ingestion of the test product , the mechanism of this enhanced absorption remains unclear . The aims of this double-blind study were 1 ) to evaluate lactose absorption after prolonged ingestion of yogurt and fermented-then-pasteurized milk ( FPM ) and 2 ) to assess the modification of the lactase activity of the duodenal mucosa . In 16 lactase-deficient subjects we confirmed that yogurt enhances lactose digestion , this beneficial effect being destroyed by pasteurization . Moreover , the long-term ( 8 d ) ingestion of either yogurt or FPM does not modify the results of hydrogen breath tests in comparison with a 24-h ingestion . The mucosal lactase ( Dahlquist method ) and beta-galactosidase ( ONPG method ) activities were not significantly modified by yogurt or FPM ingestion . These results suggest that in lactase-deficient subjects no adaptation occurs after eating yogurt or FPM and that the increased lactose absorption in yogurt must be mainly related to an intraluminal process We reported previously that consumption of one cup of milk ( 240 mL ) per day produced negligible symptoms in lactase-nonpersistent ( LNP ) individuals self-described as being severely lactose intolerant . We hypothesized that such LNP individuals could also tolerate two cups of milk per day if taken in two widely divided doses with food , and that psychologic factors play a role in perceptions of lactose intolerance . The Minnesota Multiphasic Personality Inventory 2 ( MMPI-2 ) was administered to 19 LNP subjects self-described as markedly lactose intolerant ( S-LNP ) , 13 LNP subjects who denied lactose intolerance ( A-LNP ) , and 10 lactase-persistent individuals who believed they were lactose intolerant ( S-LP ) . Symptoms were recorded when LNP subjects ingested 240 mL regular or lactose-hydrolyzed milk twice daily for 7 d in a double-blind crossover study . The results showed that neither LNP group had a significant increase in symptoms ( P < 0.05 ) during the regular compared with the lactose-hydrolyzed milk periods . However , S-LNP subjects reported significantly greater gaseous symptoms than did the A-LNP subjects during both treatment periods . The MMPI-2 showed a high score on the " lie " validity scale for S-LNP subjects . We conclude that LNP subjects tolerate two cups of milk per day without appreciable symptoms . S-LNP subjects have underlying flatulence that is misattributed to lactose intolerance . MMPI-2 results were of question able validity because of the high rate of dissimulation by LNP subjects Milk intolerance was investigated in 87 healthy elderly individuals with a mean age of 77 years who were given 240 ml of a chocolate dairy drink twice in one week with a light lunch . No significant differences in symptomatic responses distinguished the subjects consuming a lactose-free ( LF ) drink from those consuming a drink containing 4.5 % lactose ( LC ) under double-blind study conditions . Breath hydrogen analysis during lactose tolerance testing identified 23 malabsorbers , none of whom responded exclusively to the LC drink , although five were symptomatic on both days , and two had symptoms only on the day the LF drink was served . A similar percentage of absorbers ( 72 % ) and malabsorbers ( 70 % ) were asymptomatic on both days . Factors other than lactose malabsorption appeared to be responsible for the symptoms of intolerance reported , and most may have been psychosomatic in origin By ultrafiltration of skim milk a new low-lactose milk powder was developed whose lactose content was reduced by 86 % . The lactose was replaced by malto-dextrin . In contrast to lactose-hydrolyzed milk powder , no protein-destroying processes ( Maillard reactions ) could be demonstrated during production or after storage at st and ard conditions . Tolerance of the new low-lactose milk versus regular skim milk was tested in 35 well-nourished , adult Latin Americans with lactose malabsorption . The ingestion of 500 ml of the low-lactose milk gave rise to significantly ( p less than 0.05 ) fewer symptoms than regular skim milk . After the intake of 250 ml there a tendency to fewer symptoms after the low-lactose milk , although the difference was not significant ( 0.05 less than p less than 0.1 ) . The new milk may be of potential usefulness in the treatment of protein calorie malnutrition in the developing countries , where lactose malabsorption is highly prevalent Objective : To study tolerance to lactose in milk chocolate among symptomatic lactose maldigesters . Design : R and omized cross-over study .Subjects : Twenty-seven adult lactose maldigesters with symptomatic lactose intolerance . Methods : A 100 g chocolate sample prepared with whole milk ( 12 g lactose ) , whole-milk powder ( 12 g lactose ) , low-lactose milk powder ( 2 g lactose ) or lactose-free milk powder was eaten after an overnight fast . Gastrointestinal symptoms ( flatulence , abdominal bloating , abdominal pain , borgorygmi and nausea ) were recorded in a question naire during the following 8 h. Bowel movements and stool consistency were also registered during the test day . Results : The numbers of persons reporting different gastrointestinal symptoms or any of the symptoms did not differ significantly after eating the chocolate sample s. No statistical differences were found in the estimated strength of the different symptoms or the total strength of all symptoms combined . Differences in the bowel frequency and stool consistency were also non-significant . Conclusions : Lactose malabsorbers with self-reported lactose intolerence did not differ in their response to milk chocolate sample s containing different amounts of lactose Microbial-derived β-galactosidase ( β-gal ) enzyme preparations improvein vivo lactose digestion and tolerance through enhanced gastrointestinal digestion of lactose . Three different β-gal preparations , Lactogest ( soft gel capsule ) , Lactaid ( caplet ) , and DairyEase ( chewable tablet ) and placebo were fed to lactose maldigesters with either 20 g or 50 g of lactose to compare the efficacy of these products and to further establish a dose-response relationship for use . All enzyme preparations dramatically reduced both the peak and total breath hydrogen production when fed with milk containing 20 g of lactose . Four capsules of Lactogest , two caplets of Lactaid , or two tablets of DairyEase ( each treatment containing approx 6000 IU ) reduced total hydrogen production significantly ( P<0.05 ) below that observed with two capsules of Lactogest ( containing approx 3000 IU ) in a stoichiometric manner . Symptoms were significantly ( P<0.05 ) less severe with all the β-gal products . In contrast , with 50 g of lactose in water , peak and total hydrogen production was modestly , but not significantly reduced by the enzyme treatment . Furthermore , symptom scores for bloating , cramping , nausea , pain , diarrhea , and flatus were not different between treatments and the control . The 50-g lactose dose appeared to overwhelm the ability of either 3000 or 6000 IU of β-gal to assist significantly with lactose digestion . Results from these studies demonstrate the relative equivalency of chewable , caplet , and soft-get β-gal products , based on IUs of enzyme fed Background —Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption . Adaptation of the colonic flora might explain this improvement . Aims —To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose . Methods —Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15 . Between these days they were given 34 g of lactose or sucrose per day , in a double blind protocol . Stool sample s were obtained on days 0 and 14 , to measure faecal β-galactosidase and pH. Symptoms , breath H2 excretion , faecal weight and electrolytes , and orofaecal transit time were assessed . Results —Except for faecal weight , symptoms were significantly milder during the second challenge in both groups , and covariance analysis showed no statistical difference between them . In the lactose group , but not in the sucrose group , faecal β-galactosidase activity increased , pH dropped , and breath H2 excretion decreased . Conclusion —Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days , and all symptoms except diarrhoea regressed . Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation . This suggests that improved clinical tolerance may be just a placebo effect The causal relationship between lactose ingestion and gastrointestinal symptoms is question able . The aim of this study was to assess symptoms associated with milk ingestion in children with lactose maldigestion . Thirty children ( 11 males ) age 3 to 17 years with lactose maldigestion were studied . In a double-blind , crossover design , subjects ingested 240 m L daily of either lactose-hydrolyzed or lactose-containing milk for 14 days . Diaries were kept daily that recorded diet , medication use , and symptoms . There was a significant increase in abdominal pain experienced by study participants during the lactose ingestion period when compared to the lactose-free period . We conclude that ingestion of 12 g of lactose daily is associated with increased abdominal pain in susceptible children with lactose maldigestion . A trial of dietary lactose restriction may be beneficial in reducing abdominal pain in children with lactose maldigestion Using an improved double-blind test procedure , the relationship between lactose malabsorption and lactose intolerance was investigated in 87 healthy teenagers ( 14 - -19 years old ) of differing ethnic background s. Capillary blood glucose analysis after an oral dose of 50 g of lactose identified 45 lactose malabsorbers . A lactose-free ( LF ) chocolate dairy drink and one containing 4.5 % lactose ( LC ) were administered under double-blind conditions on 4 consecutive mornings . As in a similar prior study , no statistically significant differences were found in the incidence of symptoms reported by malabsorbers and absorbers after drinking 240 ml of either the LF or the LC preparation . However , 12 lactose absorbers reported symptoms apparently not due to lactose , i.e. , after 240 ml of LF , after this amount of both LF and LC , or after 240 ml ( but not 480 ml ) of LC . Such false-positive results would only be identified by the double-blind approach . It did not appear that any of the malabsorbers had symptoms due to the lactose in 240 ml of LC . However , 16 % of the malabsorbers apparently reacted to the lactose in 480 ml of LC . Well design ed , double-blind clinical trials are essential for evaluation of gastrointestinal responses to lactose or other ingredients in milk Eighty Italian adults ( 53 females , 18 - 69 years , and 27 males , 18 - 60 years ) underwent double-blind tests involving the intake of increasing amounts ( 125 , 250 , 500 , 1000 ml/d ) of four types of milk with normal or low lactose and /or fat content . The tests were completed satisfactorily by 71 subjects . Forty were lactose malabsorbers ( LMs ) and 31 were absorbers ( LAs ) , according to a st and ard oral lactose tolerance test . Each subject reported on a question naire whether he/she experienced symptoms during the 24 h after milk intake , and the intensity of the symptoms , adopting a score of 0 to 12 , according to an already tested procedure . The aim of the study was to investigate the relationship between lactose malabsorption or absorption and intolerance to milk in Italian adults , relative to lactose and fat contents , dose of milk and individual sensitivity . LMs reported symptoms overall more frequently and with greater intensity than LAs ( P less than 0.001 ) . The amount of milk ingested was positively associated with the frequency of symptoms both in LMs and LAs . Contrary to earlier findings , fat seemed to contribute to milk intolerance in LMs rather than to reduce it . According to analysis of variance individual differences accounted for 40 per cent of total variation in symptom frequency The addition of microbial beta-galactosidases directly to milk at mealtime represents a potential " enzyme replacement therapy " for primary lactase deficiency . We used the hydrogen breath test as the index of incomplete carbohydrate absorption to assess the efficacy of two enzymes -- one from yeast , Kluyveromyces lactis ( LactAid ) , and the other from the fungus Aspergillus niger ( Lactase N)--to assist in the hydrolysis of 18 g of lactose in 360 ml ( 12 oz ) of whole milk when consumed by an adult lactose malabsorber . Grade d amounts of Lactase N produced , at best , a 53 % relative reduction in breath hydrogen excretion , whereas quantitative elimination of excess hydrogen excretion was produced by 1 and 1.5 g of LactAid . A double-blind , controlled , crossover trial was subsequently performed in 50 healthy , unselected Mexican adults , to whom 360 ml of cow 's milk was presented in the three forms in a r and omized order : intact milk , prehydrolyzed milk , and milk to which 1 g of LactAid was added immediately before consumption . Among the 25 subjects with incomplete carbohydrate absorption with intact milk , adding enzyme 5-min before consumption produced a 62 % reduction in breath hydrogen excretion , and symptoms of intolerance were significantly reduced . The feasibility of effective enzyme replacement therapy with a beta-galactosidase from K. lactis is demonstrated BACKGROUND Abdominal symptoms linked to lactose malabsorption may be caused by metabolic activity of colonic bacteria . Rifaximin , a non-absorbable rifampycin derivative , is active against colonic bacteria , it may be useful in the treatment of lactose intolerance . AIM The aim of this study has been to evaluate short-term rifaximin therapy in patients with lactose intolerance . METHODS Thirty-two patients with lactose intolerance diagnosed using the hydrogen lactose breath test were studied . Fourteen patients received rifaximin 800 mg/day for 10 days , 13 patients followed a diet without milk for 40 days and 5 patients received a placebo for 10 days . Total breath H(2 ) excretion expressed as area under the curve , and the symptom score were evaluated in all patients at the start , and subsequently after 10 and 40 days . RESULTS In the 14 patients who received rifaximin for 10 days , area under the curve at day 10 and day 40 was statistically significantly lower than the one computed at basal ( P<0.01 ) . Diet reduced area under the curve progressively reaching statistical significance at day 40 , while the placebo did not change area under the curve throughout the study . The total symptom score significantly improved after rifaximin and diet . CONCLUSION In patients with lactose intolerance , a 10-day therapy with rifaximin as well as 40-day diet without lactose reduces the area under the curve and the symptom score Objective : This study investigated the role of the fat content of milk on symptoms of lactose intolerance . Design : Subjects recorded intolerance symptoms using a visual analogue scale ( VAS ) following ingestion of three test milks of varying fat content for a two-day period . Subjects/ Setting : The subjects were thirty adult volunteers , patients of two Estonian out-patient clinics with diagnosed lactose intolerance . The study milks were drunk at home or at work . All thirty subjects completed the study protocol . Intervention : Each subject drank , in r and om order , fat-free milk ( 4.9 % lactose ) , high-fat milk ( 8 % fat , 4.9 % lactose ) , and a lactose-free and fat-free control milk . They drank 200 ml of the milk twice a day for two days , one milk type per session , with five days between sessions . The subjects noted their gastrointestinal symptoms during the test periods and during a 5 d milk-free period at the beginning of the study . The occurrence and severity of symptoms were compared . A global measure of the severity of symptoms was defined by computing the sum of the symptom scores . Results : The sum of symptoms was higher during all milk periods than during the milk-free period ( P<0.01 ) . There were no statistically significant differences in the occurrence or severity of symptoms during the fat-free milk period compared with the high-fat milk period . Conclusions : Even a marked difference in the fat content of milk did not affect the symptoms of lactose intolerance . Consequently , there seems to be no case for recommending full-fat milk products in the treatment of lactose intolerance . Sponsorship : The study was supported by the Foundation of the Finnish Association of Agronomists : Valio Ltd , Finl and , provided the test milks Fifteen lactose malabsorbers were studied to evaluate the effects of consumption of milk containing different strains of Bifidobacterium longum on lactose digestion . Influences of different growth substrates , bile sensitivity , and lactose transport on lactose digestion by bifidobacteria were also investigated . Lactose malabsorption was determined by measuring breath hydrogen excretion of subjects fed four different test milks ( three of which contained 5 x 10(8 ) cfu/ml of B. longum ) on 4 different d using a r and omized , double-blinded trial . Test milks included 1 ) 400 ml of lowfat milk ( control ) , 2 ) 400 ml of milk containing B. longum B6 that had been grown with lactose , 3 ) 400 ml of milk containing B. longum B6 grown with lactose plus glucose , or 4 ) 400 ml of milk containing B. longum ATCC 15708 grown with lactose . beta-Galactosidase activity was highest in milk containing B6 grown with lactose but was extremely low in milk containing B6 grown with lactose and glucose . Consumption of milk containing B6 grown with lactose result ed in significantly less hydrogen production and flatulence than occurring after consumption of control milk or the milk containing B6 grown with both lactose and glucose . Hydrogen production after ingestion of 15708 was also significantly lower than hydrogen production after ingestion of the control milk . We concluded that milks containing B. longum might reduce breath hydrogen response and symptoms from lactose malabsorption when the culture is grown in a medium containing only lactose to induce a higher beta-galactosidase level and increase rate of lactose uptake BACKGROUND Ingestion of a large dose of the milk sugar lactose -- for example , the 50-g load in 1 liter of milk -- causes symptoms such as abdominal pain , diarrhea , bloating , and flatulence in the majority of people with lactose malabsorption . It is uncertain whether the ingestion of more common doses of lactose , such as the amount in 240 ml ( 8 oz ) of milk , causes symptoms . Some people insist that even smaller quantities of milk , such as the amount used with cereal or coffee , cause severe gastrointestinal distress . METHODS In a r and omized , double-blind , crossover trial , we evaluated gastrointestinal symptoms in 30 people ( mean age , 29.4 years ; range , 18 to 50 ) who reported severe lactose intolerance and said they consistently had symptoms after ingesting less than 240 ml of milk . The ability to digest lactose was assessed by measuring the subjects ' end-alveolar hydrogen concentration after they ingested 15 g of lactose in 250 ml of water . Subjects then received either 240 ml of lactose-hydrolyzed milk containing 2 percent fat or 240 ml of milk containing 2 percent fat and sweetened with aspartame to approximate the taste of lactose-hydrolyzed milk ; each type of milk was administered daily with breakfast for a one-week period . Using a st and ardized scale , subjects rated the occurrence and severity of bloating , abdominal pain , diarrhea , and flatus and recorded each passage of flatus . RESULTS Twenty-one participants were classified as having lactose malabsorption and nine as being able to absorb lactose . During the study periods , gastrointestinal symptoms were minimal ( mean symptom-severity scores for bloating , abdominal pain , diarrhea , and flatus between 0.1 and 1.2 [ 1 indicated trivial symptoms ; and 2 , mild symptoms ] ) . When the periods were compared , there were no statistically significant differences in the severity of these four gastrointestinal symptoms . For the lactose-malabsorption group , the mean ( + /- SEM ) difference in episodes of flatus per day was 2.5 + /- 1.1 ( 95 percent confidence interval , 0.2 to 4.8 ) . Daily dietary records indicated a high degree of compliance , with no additional sources of lactose reported . CONCLUSIONS People who identify themselves as severely lactose-intolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance . When lactose intake is limited to the equivalent of 240 ml of milk or less a day , symptoms are likely to be negligible and the use of lactose-digestive aids unnecessary A calcium absorption investigation was carried out with the purpose of determining whether lactose-hydrolyzed milk facilitates calcium absorption in subjects with lactose malabsorption . Nine children participated in the study , which was divided into two investigation periods separated by at least 1 week . During the first period the children were given a lactose-free diet , whereas during the second period their diet contained lactose-hydrolyzed milk . The amount of calcium , number of calories , and rotation of specifically defined meals in the diet during the two periods were identical , and the children functioned as their own controls . We found calcium absorption to be significantly higher with the diet containing hydrolyzed milk than with the lactose-free diet supplemented with extra calcium ( p < 0.05 ) . During the study a double-blind lactose intolerance test was performed . The children had significantly fewer clinical symptoms and signs , such as abdominal pain , borborygmus , meteorism , and defecations , within 24 h after drinking 0.5 L of lactose-hydrolyzed milk as compared with drinking ordinary milk ( 25 g of lactose ) . None of the children experienced any unpleasant side effects when consuming the lactose-hydrolyzed milk ( approximately 94 % degree of hydrolysis ) during the study period . All the children liked the hydrolyzed milk because it had a pleasant , sweet flavor as a result of the increased content of glucose The influence of bile sensitivity , lactose transport , and acid tolerance of Lactobacillus acidophilus on in vivo digestion of lactose was investigated . Four strains of L. acidophilus exhibiting varied degrees of lactose transport , beta-galactosidase activity , and bile sensitivity were used to prepare unfermented acidophilus milks . Lactose malabsorption was evaluated by measuring breath H2 excretion off 11 lactose maldigesting subjects following ingestion of four acidophilus test milks . Test meals were fed in a r and omized double-blind protocol . Consumption of acidophilus milk ( 2 % fat ) containing strains B , N1 , and E significantly reduced mean total H2 production compared with that of the control reduced-fat ( 2 % fat ) milk , but milk containing strain ATCC 4356 did not differ from the control . Acidophilus milk containing L. acidophilus N1 was the most effective of the four acidophilus milks in improving lactose digestion and tolerance . Strain N1 exhibited the lowest beta-galactosidase activity and lactose transport but the greatest bile and acid tolerance of the four strains . The results indicated that bile and acid tolerance may be important factors to consider when L. acidophilus strains are selected for improving lactose digestion and tolerance Eleven lactose-intolerant patients were investigated in a double-blind crossover controlled study . In r and om sequence they received 500 ml of either ordinary cow milk ( lactose content , 25 g ) or the same amount of low-lactose milk ( 85 % of the lactose hydrolyzed ) , which had been processed by Lactozym 3000 L for 24 h at 4 degrees C. A significantly increased blood glucose rise from fasting levels was demonstrated in the low-lactose tests . Similarly , a significant reduction of liquid stool frequency , abdominal colics , distention , borborrhygmia , and flatulence was demonstrated . It was concluded that further studies , including long-term treatment of lactose-intolerant children , are indicated |
448 | 26,611,943 | Overall , oral CHM used as a monotherapy or as an adjunct to conventional therapies appears safe , and it may improve subjective sleep in people with insomnia .
However , the typical effect of CHM for insomnia can not be determined due to heterogeneity . | This systematic review is to evaluate the efficacy and safety of Chinese herbal medicine ( CHM ) for people with insomnia . | Controlled trials that use r and omized allocation are the best tool to control for bias and confounding in trials testing clinical interventions . Investigators must be sure to include information that is required by the reader to judge the validity and implication s of the findings in the reports of these trials . In part , complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes . The consoli date d st and ards of reporting trials ( CONSORT ) statement was developed to assist investigators , authors , review ers , and editors on the necessary information to be included in reports of controlled clinical trials . The CONSORT statement is applicable to any intervention , including herbal medicinal products . Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT . Recently , reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for r and omized controlled trials of herbal medicines . We expect that these recommendations will lead to more complete and accurate reporting of herbal trials . We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration , together with examples of good reporting and empirical evidence , where available , for each . These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected BACKGROUND Clear , transparent , and sufficiently detailed abstract s of conferences and journal articles related to r and omized controlled trials ( RCTs ) are important , because readers often base their assessment of a trial solely on information in the abstract . Here , we extend the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement to develop a minimum list of essential items , which authors should consider when reporting the results of a RCT in any journal or conference abstract . METHODS AND FINDINGS We generated a list of items from existing quality assessment tools and empirical evidence . A three-round , modified-Delphi process was used to select items . In all , 109 participants were invited to participate in an electronic survey ; the response rate was 61 % . Survey results were presented at a meeting of the CONSORT Group in Montebello , Canada , January 2007 , involving 26 participants , including clinical trialists , statisticians , epidemiologists , and biomedical editors . Checklist items were discussed for eligibility into the final checklist . The checklist was then revised to ensure that it reflected discussion s held during and subsequent to the meeting . CONSORT for Abstract s recommends that abstract s relating to RCTs have a structured format . Items should include details of trial objectives ; trial design ( e.g. , method of allocation , blinding/masking ) ; trial participants ( i.e. , description , numbers r and omized , and number analyzed ) ; interventions intended for each r and omized group and their impact on primary efficacy outcomes and harms ; trial conclusions ; trial registration name and number ; and source of funding . We recommend the checklist be used in conjunction with this explanatory document , which includes examples of good reporting , rationale , and evidence , when available , for the inclusion of each item . CONCLUSIONS CONSORT for Abstract s aims to improve reporting of abstract s of RCTs published in journal articles and conference proceedings . It will help authors of abstract s of these trials provide the detail and clarity needed by readers wishing to assess a trial 's validity and the applicability of its results Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports Abstract Medical treatment is usually accompanied by a warning about potential side effects . While constituting an important component of informed consent , these warnings may themselves contribute to side effects via the placebo effect . We tested this possibility using a 2 × 2 between-subjects design . Under the guise of a trial of a new hypnotic , 91 undergraduates experiencing difficulty sleeping were allocated to receive a warning about a target side effect ( either increase or decrease in appetite , counterbalanced ) or no warning and then to receive placebo treatment or no treatment for one week . Placebo treatment led to significantly better sleep on almost all self-reported outcomes , suggesting a placebo effect for reported sleep difficulty . Actigraphy recordings were unaffected by treatment . There was a clear effect of the warning in that placebo treated participants who were warned about side effects were much more likely to report the target side effect than those not warned about side effects . Implication s for clinical practice are discussed CONTEXT Cognitive behavioral therapy ( CBT ) and hypnotic medications are efficacious for short-term treatment of insomnia , but few patients achieve complete remission with any single treatment . It is unclear whether combined or maintenance therapies would enhance outcome . OBJECTIVES To evaluate the added value of medication over CBT alone for acute treatment of insomnia and the effects of maintenance therapies on long-term outcome . DESIGN , SETTING , AND PATIENTS Prospect i ve , r and omized controlled trial involving 2-stage therapy for 160 adults with persistent insomnia treated at a university hospital sleep center in Canada between January 2002 and April 2005 . INTERVENTIONS Participants received CBT alone or CBT plus 10 mg/d ( taken at bedtime ) of zolpidem for an initial 6-week therapy , followed by extended 6-month therapy . Patients initially treated with CBT attended monthly maintenance CBT for 6 months or received no additional treatment and those initially treated with combined therapy ( CBT plus 10 mg/d of zolpidem ) continued with CBT plus intermittent use of zolpidem or CBT only . MAIN OUTCOME MEASURES Sleep onset latency , time awake after sleep onset , total sleep time , and sleep efficiency derived from daily diaries ( primary outcomes ) ; treatment response and remission rates derived from the Insomnia Severity Index ( secondary outcomes ) . RESULTS Cognitive behavioral therapy used singly or in combination with zolpidem produced significant improvements in sleep latency , time awake after sleep onset , and sleep efficiency during initial therapy ( all P<.001 ) ; a larger increase of sleep time was obtained with the combined approach ( P = .04 ) . Both CBT alone and CBT plus zolpidem produced similar rates of treatment responders ( 60 % [ 45/75 ] vs 61 % [ 45/74 ] , respectively ; P = .84 ) and treatment remissions ( 39 % [ 29/75 ] vs 44 % [ 33/74 ] , respectively ; P = .52 ) with the 6-week acute treatment , but combined therapy produced a higher remission rate compared with CBT alone during the 6-month extended therapy phase and the 6-month follow-up period ( 56 % [ 43/74 and 32/59 ] vs 43 % [ 34/75 and 28/68 ] ; P = .05 ) . The best long-term outcome was obtained with patients treated with combined therapy initially , followed by CBT alone , as evidence d by higher remission rates at the 6-month follow-up compared with patients who continued to take zolpidem during extended therapy ( 68 % [ 20/30 ] vs 42 % [ 12/29 ] ; P = .04 ) . CONCLUSION In patients with persistent insomnia , the addition of medication to CBT produced added benefits during acute therapy , but long-term outcome was optimized when medication is discontinued during maintenance CBT . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00042146 Background . The increased practice of traditional Chinese medicine ( TCM ) worldwide has raised concerns regarding herb-drug interactions . The purpose of our study is to analyze the concurrent use of Chinese herbal products ( CHPs ) among Taiwanese insomnia patients taking hypnotic drugs . Methods . The usage , frequency of services , and CHP prescribed among 53,949 insomnia sufferers were evaluated from a r and om sample of 1 million beneficiaries in the National Health Insurance Research Data base . A logistic regression method was used to identify the factors that were associated with the coprescription of a CHP and a hypnotic drug . Cox proportional hazards regressions were performed to calculate the hazard ratios ( HRs ) of hip fracture between the two groups . Results . More than 1 of every 3 hypnotic users also used a CHP concurrently . Jia-Wei-Xiao-Yao-San ( Augmented Rambling Powder ) and Suan-Zao-Ren-Tang ( Zizyphus Combination ) were the 2 most commonly used CHPs that were coadministered with hypnotic drugs . The HR of hip fracture for hypnotic-drug users who used a CHP concurrently was 0.57-fold ( 95 % CI = 0.47–0.69 ) that of hypnotic-drug users who did not use a CHP . Conclusion . Exploring potential CHP-drug interactions and integrating both healthcare approaches might be beneficial for the overall health and quality of life of insomnia sufferers PURPOSE Drug utilization studies are important for the optimization of drug therapy and have received a great attention in recent years . Most of the information on drug use patterns has been derived from studies in modern Western medicines ; however , studies regarding the drug utilization of traditional Chinese medicine ( CM ) are few . The present study was the first clinical research to evaluate the drug utilization patterns of Chinese herbal medicines in a general hospital in Taiwan . METHODS Data were collected prospect ively from the patients attending the Traditional Medicine Center of Taipei Veteran General Hospital under CM drug treatments . The study was carried out over a period of 1 year , from January 2002 to December 2002 . Core drug use indicators , such as the average number of drugs per prescriptions , the dosing frequency of prescriptions , and the most common prescribed CM herbs and formulae were evaluated . The primary diagnosis and the CM drugs prescribed for were also revealed . All data were analyzed by descriptive statistics . RESULTS A total of 10 737 patients , representing 52 255 CM drugs , were screened during the study period . Regarding the prescriptions , the average number of drugs per prescription was 4.87 and 37.21 % of prescriptions were composed by five drugs . Most of prescriptions ( 91.38 % ) were prescribed for three times a day . The most often prescribed Chinese herb was Hong-Hwa ( 5.76 % ) and the most common Chinese herbal formula was Jia-Wey-Shiau-Yau-San ( 3.80 % ) . The most frequent main diagnosis was insomnia ( 15.58 % ) , followed by menopause ( 5.22 % ) and constipation ( 5.09 % ) . CONCLUSION The survey revealed the drug use pattern of CMs in a general hospital . The majority of CM prescriptions were composed by 3 - 6 drugs and often prescribed for three times a day . Generally , the rational drug uses of CM drugs were provided with respect to the various diagnoses OBJECTIVE To subjectively and objective ly assess the effect of Jiawei Xiaoyao Powder ( JXYP ) on sleep in patients with psychological stress insomnia . METHHODS : A r and omized controlled study was conducted in 33 patients with psychological stress insomnia . They were assigned to 4 groups , 4 in the TCM group treated with JXYP , 5 in the Western medicine ( WM ) group treated with Estazolam , 9 in the integrated medicine ( IM ) group treated with JXYP plus Estazolam , and 10 in the control group treated with placebo . Quality of sleep in patients was assessed subjectively and objective ly before treatment and 6 weeks after treatment by Pittsburgh sleep quality index ( PSQI ) , self-rating scale of sleep ( SRSS ) and polysomnography ( PSG ) , respectively . RESULTS Subjective assessment on sleep showed that after 6-week treatment , the scores of PSQI and SRSS remarkably reduced in the TCM , IM and control groups ( P < 0.05 ) , while the decrease was insignificant in the WM group ( P > 0.05 ) , but no significant difference between groups was shown . The objective assessment by PSG showed that no significant change was found after treatment in parameters of total sleep time ( TST ) , sleep time of phase 1 and 2 , slow wave phase , rapid-eye-movement ( REM ) phase , sleep latency , REM sleep latency , also in long waking and short waking times in all group ( P > 0.05 ) , but a significant increase of sleep efficacy ( P < 0.05 ) and an increasing trend of TST ( P > 0.05 ) were shown in the IM group , and an increasing trend of both in the TCM group ( P > 0.05 ) . CONCLUSION JXYP , combined with or without Estazolam , can improve the quality of sleep subjectively , and the combination of the two could enhance the efficacy of sleep in patients with psychological stress insomnia ETHNOPHARMACOLOGICAL RELEVANCE Wuling Capsule is a single herbal formula from mycelia of precious Xylaria nigripes ( Kl . ) Sacc and its pharmacological function have a tranquilizing effect on the central nervous system . The aim of the study to evaluate the efficacy and safety of Wuling capsule in treatment of insomnia . MATERIAL S AND METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled study . The participants received either placebo ( n=92 ) or Wuling capsule ( n=94 ) for 4 weeks and a follow-up period for 2 weeks . RESULTS Compared between pre-treatment and post-treatment , the global Pittsburgh sleep quality index ( PSQI ) scores in both Wuling capsule group and placebo group improved significantly ( P<0.01 ) . However , there was no significant difference between Wuling capsule group and placebo group ( P>0.05 ) . Scores of clinical global impressions scale ( CGI-I ) at each week in Wuling capsule group was similar to those in placebo group ( P>0.05 ) . Compared between pre-treatment and post-treatment , scores of the four components of world health organization on quality of life brief scale ( WHOQOL-BREF ) in both Wuling capsule group and placebo group improved significantly ( P<0.01 ) . However , there were no difference between the two groups ( P>0.05 ) . The rate of adverse events was 10.10 % in Wuling group , and 6.73 % in placebo group ( P>0.05 ) . CONCLUSIONS Wuling capsule can improve insomnia when compared with pre-treatment for 4 weeks and be a well tolerated by all the patients at the 6 weeks of study period . However , there are no significant in the results of the variables tested when compared with placebo control . Further additional rigorous r and omized clinical trials are still required OBJECTIVE To evaluate the therapeutic effects and safety of the XIA 's No.1 Sleeping Prescription for the treatment of insomnia of the deficiency type . METHODS 120 cases conformed to the diagnostic criteria of the Chinese Classification of Mental Disorders-Version 3 ( CCMD-3 ) and were diagnosed as having insomnia of the deficiency type were divided r and omly into a treatment group and a control group , 60 cases in each group . The treatment group was treated with the XIA 's No. 1 Sleeping Prescription , while the control group was given estazolam ( 1 mg ) for 6 weeks . The Athens Insomnia Scale ( AIS ) was used to evaluate the clinical therapeutic effects , while the treatment emergent symptom scale ( TESS ) was used to evaluate adverse reactions . RESULTS The total effective rate of the treatment group ( 80 % ) was higher than that of the control group ( 70 % ) , but with no significant difference ( P > 0.05 ) . The effective rate for long-term insomnia was 77.8 % in the treatment group and 52.4 % in the control group , with a significant difference between the two groups ( P < 0.05 ) . The adverse reactions shown in the treatment group were obviously fewer and milder than those in the control group . CONCLUSION The XIA 's No. 1 Sleeping Prescription is effective for insomnia of the deficiency type and with no obvious toxic side effects Background : Insomnia is a prevalent health complaint that is often difficult to evaluate reliably . There is an important need for brief and valid assessment tools to assist practitioners in the clinical evaluation of insomnia complaints . Objective : This paper reports on the clinical validation of the Insomnia Severity Index ( ISI ) as a brief screening measure of insomnia and as an outcome measure in treatment research . The psychometric properties ( internal consistency , concurrent validity , factor structure ) of the ISI were evaluated in two sample s of insomnia patients . Methods : The first study examined the internal consistency and concurrent validity of the ISI in 145 patients evaluated for insomnia at a sleep disorders clinic . Data from the ISI were compared to those of a sleep diary measure . In the second study , the concurrent validity of the ISI was evaluated in a sample of 78 older patients who participated in a r and omized-controlled trial of behavioral and pharmacological therapies for insomnia . Change scores on the ISI over time were compared with those obtained from sleep diaries and polysomnography . Comparisons were also made between ISI scores obtained from patients , significant others , and clinicians . Results : The results of Study 1 showed that the ISI has adequate internal consistency and is a reliable self-report measure to evaluate perceived sleep difficulties . The results from Study 2 also indicated that the ISI is a valid and sensitive measure to detect changes in perceived sleep difficulties with treatment . In addition , there is a close convergence between scores obtained from the ISI patient 's version and those from the clinician 's and significant other 's versions . Conclusions : The present findings indicate that the ISI is a reliable and valid instrument to quantify perceived insomnia severity . The ISI is likely to be a clinical ly useful tool as a screening device or as an outcome measure in insomnia treatment research Midazolam ( 15 mg ) was compared with temazepam ( 30 mg ) in a r and omized , double-blind , parallel group study . An initial screening period was followed by 3 days of placebo baseline , 4 to 12 weeks of nightly oral use of the medication and a 4-day placebo withdrawal period . One hundred seventy-five patients with chronic insomnia participated in this multicenter outpatient study . Because the elimination half-life of midazolam , a new trizolobenzodiazepine hypnotic , is short ( 1.3 - 2.2 hr ) compared to temazepam 's ( 12 - 16 hr ) , more problems with tolerance and rebound insomnia were expected to occur . Hypnotic efficacy ( increased total sleep time , decreased wake time , and decreased sleep latency ) was demonstrated for both medications over the entire 3-month period without the development of tolerance . In fact , if anything , efficacy increased with time on medication , suggesting possible facilitation or " inverse tolerance " effect . On withdrawal , sleep was improved compared with baseline , suggesting partial resolution of the insomniac condition rather than rebound insomnia . These effects were both statistically and clinical ly significant for midazolam , with 16 % to 50 % improvement in sleep measures . The results of this study suggest that patients with chronic insomnia may benefit from 30 to 90 days of treatment . A three-factor model that separates pharmacologic from behavioral and psychologic effects of hypnotics was proposed to explain these results in part This article explores the efficacy of sequential treatment involving medication and cognitive behavioral treatment ( CBT ) for insomnia . In a multiple baseline across-subjects design , 6 participants with primary chronic insomnia received 1 of the following treatment sequences : ( a ) concurrent combination of medication and CBT for the 10-week treatment duration ( Combined ) ; ( b ) medication for the first 5 weeks , with introduction of CBT at week 4 and medication withdrawal after the 5th week result ing in treatment overlap during weeks 4 and 5 ( Overlapping : Medication → Combined → CBT ) ; and ( c ) medication alone for the first 5 weeks followed by CBT alone for an additional 5 weeks ( Medication → CBT ) . Each sequence led to significant sleep improvements , but these improvements occurred at different times during the intervention . Participants in the Combined and in the Overlapping sequences improved their sleep during the 1st phase of treatment , whereas those in the Medication → CBT sequence improved mostly during the 2nd phase of treatment . These preliminary results suggest that a sequential treatment is effective for chronic insomnia . In addition , the results suggest that sleep improvements are more likely to emerge when CBT is introduced , with an Overlapping sequence showing a slight advantage over the other sequences . Additional clinical trials should be conducted with larger sample s to replicate these preliminary findings OBJECTIVE To observe the effect of Zaoren Anshen capsules in treating senile insomnia and changes in its hemorheology . METHOD A total of 120 patients with senile insomnia were r and omly divided into the Zaoren Anshen capsules group ( five capsules , n = 60 ) and the Alprazolam group ( 0.8 mg , n = 60 ) for treatment and control observation . Pittsburgh sleep quality index ( PSQI ) was used for evaluating clinical efficacy in the first and fourth week before and after treatment . RESULT The Zaoren Anshen capsules group had lower higher scores in PSQI ( 5.91 + /- 1.37 ) than that before treatment ( 13.49 + /- 3.87 ) , with great statistical significant in difference ( P < 0.01 ) . The alprazolam group had lower higher scores in PSQI than that before treatment , with great statistical significant in difference ( P < 0.01 ) . apart from higher PSQI scores in the Zaoren Anshen capsules group than that of the Alprazolam group after treatment for one week ( P < 0.05 ) , the comparison between the Zaoren Anshen capsules group and the alprazolam group before and after treatment for four weeks showed no statistical significance . As for hemorheological parameters , the difference in the whole blood viscosity ( including high-shear , middle-shear and low-shear ) of patients in the Zaoren Anshen capsules showed great statistical significance before and after treatment ( P < 0.01 ) , and so did the plasma viscosity ( P < 0.05 ) . Zaoren Anshen capsules showed less adverse reactions than alprazolam . CONCLUSION Zaoren Anshen capsules have similar effect in treating senile insomnia with alprazolam , with less adverse reactions . They are so suitable for patients with senile insomnia that they can improve hemorheological indicators of patients with senile insomnia and have good effect in promoting circulation and removing stasis |
449 | 31,216,498 | In contrast , the benefits of sleep are significantly greater when the likelihood of spontaneous retrieval is high ( d = 0.94 , CI95 = 0.44 - 1.44 ) versus low ( d = 0.45 , CI95 = -0.02 - 0.93 ) , suggesting that sleep may leverage on spontaneous retrieval processes to improve PM . | Prospect i ve memory ( PM ) enables us to execute previously conceived intentions at a later time and is used when remembering to call a friend or su bmi tting a proposal on time .
Evidence that sleep benefits PM is presently mixed .
Further , when a benefit is observed , it is unclear if this is achieved through improvements in strategic monitoring ( maintaining an intention in mind and search ing for cues ) or spontaneous retrieval ( an automatic process occurring without preparatory attention ) . | Background Prospect i ve memory ( PM ) denotes the ability to remember to perform actions in the future . It has been argued that st and ard laboratory paradigms fail to capture core aspects of PM . Methodology /Principal Findings We combined functional MRI , virtual reality , eye-tracking and verbal reports to explore the dynamic allocation of neurocognitive processes during a naturalistic PM task where individuals performed err and s in a realistic model of their residential town . Based on eye movement data and verbal reports , we modeled PM as an iterative loop of five sustained and transient phases : intention maintenance before target detection ( TD ) , TD , intention maintenance after TD , action , and switching , the latter representing the activation of a new intention in mind . The fMRI analyses revealed continuous engagement of a top-down fronto-parietal network throughout the entire task , likely subserving goal maintenance in mind . In addition , a shift was observed from a perceptual ( occipital ) system while search ing for places to go , to a mnemonic ( temporo-parietal , fronto-hippocampal ) system for remembering what actions to perform after TD . Updating of the top-down fronto-parietal network occurred at both TD and switching , the latter likely also being characterized by frontopolar activity . Conclusion / Significance Taken together , these findings show how brain systems complementary interact during real-world PM , and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspect i ve MEmory DYnamic ( PROMEDY ) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks Memories are of the past but for the future , enabling individuals to implement intended plans and actions at the appropriate time . Prospect i ve memory is the specific ability to remember and execute an intended behavior at some design ated point in the future . Although sleep is well-known to benefit the consolidation of memories for past events , its role for prospect i ve memory is still not well understood . Here , we show that sleep as compared to wakefulness after prospect i ve memory instruction enhanced the successful execution of prospect i ve memories two days later . We further show that sleep benefited both components of prospect i ve memory , i.e. to remember that something has to be done ( prospect i ve component ) and to remember what has to be done ( retrospective component ) . Finally , sleep enhanced prospect i ve remembering particularly when attentional re sources were reduced during task execution , suggesting that subjects after sleep were able to recruit additional spontaneous-associative retrieval processes to remember intentions successfully . Our findings indicate that sleep supports the maintenance of prospect i ve memory over time by strengthening intentional memory representations , thus favoring the spontaneous retrieval of the intended action at the appropriate time BACKGROUND Recent findings suggest that there may be a relationship between excessive daytime sleepiness ( EDS ) and cognitive deficits . This study aims to determine to what extent EDS is predictive of cognitive impairment in an elderly population . METHODS A total of 1026 individuals 60 years or older representative of the general population living in the metropolitan area of Paris , France , were interviewed by telephone using the Sleep-EVAL expert system . To find these individuals , 7010 r and omly selected households were called : 1269 had at least 1 household member in this age range ( participation rate , 80.9 % ) . In addition to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and International Classification of Sleep Disorders diagnoses , the system administered to participants the Psychological General Well-being Schedule , the Cognitive Difficulties Scale ( MacNair-R ) , and an independent living scale . RESULTS Excessive daytime sleepiness was reported by 13.6 % of the sample , with no significant difference among age groups . Compared with nonsleepy participants , those with EDS were at increased risk of cognitive impairment on all the dimensions of the MacNair-R scale after controlling for age , sex , physical activity , occupation , organic diseases , use of sleep or anxiety medication , sleep duration , and psychological well-being . The odd ratios were 2.1 for attention-concentration deficits , 1.7 for praxis , 2.0 for delayed recall , 2.5 for difficulties in orientation for persons , 2.2 for difficulties in temporal orientation , and 1.8 for prospect i ve memory . CONCLUSIONS Among elderly individuals in the general population , EDS is an important risk factor for cognitive impairment . A complaint of EDS by an elderly patient should signal the possibility of an underlying cognitive impairment in need of evaluation Time-based prospect i ve memory ( TBPM ) is required when it is necessary to remember to perform an action at a specific future point in time . This type of memory has been found to be particularly sensitive to ageing , probably because it requires a self-initiated response at a specific time . In this study , we sought to examine the involvement of temporal processes in the time monitoring strategy , which has been demonstrated to be a decisive factor in TBPM efficiency . We compared the performance of young and older adults in a TBPM task in which they had to press a response button every minute while categorising words . The design allowed participants to monitor time by checking a clock whenever they decided . Participants also completed a classic time-production task and several executive tasks assessing inhibition , updating and shifting processes . Our results confirm an age-related lack of accuracy in prospect i ve memory performance , which seems to be related to a deficient strategic use of time monitoring . This could in turn be partially explained by age-related temporal deficits , as evidence d in the duration production task . These findings suggest that studies design ed to investigate the age effect in TBPM tasks should consider the contribution of temporal mechanisms The aim of the present study was to deepen knowledge about the effect of a lowered vigilance state on time-based prospect i ve memory ( TBPM ) performance . For this purpose 2 TBPM tasks ( primary and interpolated ) , which shared a portion of the retention interval , and 3 reasoning tasks , as ongoing activities , were administered after total sleep deprivation and in a regular sleep condition . The results showed a detrimental effect of sleep deprivation on prospect i ve memory performance and a partial dissociation between clock-checking behavior and time estimation for prospect i ve compliance . This study clearly indicates that total sleep deprivation im- pairs the ability to complete multiple prospect i ve task assignments in a timely fashion . Results are discussed suggesting the existence of different mechanisms involved in time monitoring and other cognitive functions underlying TBPM performance Prospect i ve memory is defined as remembering to do something at a particular moment in the future and may be modulated by sleep . Here , we investigated whether multiple nights of partial sleep deprivation would affect the successful retrieval of intentions . Fifty-nine adolescents ( mean age ± SD : 16.1 ± 0.6 years ) were instructed to remember to press specific keys in response to the target words presented during a semantic categorization task in the future . Their memory was tested after five nights of either 5-h ( sleep restriction group ) or 9-h time-in-bed ( control group ) . The average percentage of target words correctly responded to was small and did not significantly differ between the two groups ( mean ± SEM for the sleep restriction group : 15.52 ± 6.61 % ; the control group : 23.33 ± 7.48 % , p = 0.44 ) . Thus , after the extended retention interval , prospect i ve remembering was poor and did not appear to be affected by post-learning sleep restriction . These findings suggest a temporal boundary beyond which intentions fall below requisite levels of activation , potentially masking any benefits for retrieval conferred by sleep OBJECTIVE The relationship between insomnia symptoms and cognitive performance is unclear , particularly at the population level . We conducted the largest examination of this association to date through analysis of the UK Biobank , a large population -based sample of adults aged 40 - 69 years . We also sought to determine associations between cognitive performance and self-reported chronotype , sleep medication use and sleep duration . METHODS This cross-sectional , population -based study involved 477,529 participants , comprising 133,314 patients with frequent insomnia symptoms ( age : 57.4 ± 7.7 years ; 62.1 % female ) and 344,215 controls without insomnia symptoms ( age : 56.1 ± 8.2 years ; 52.0 % female ) . Cognitive performance was assessed by a touchscreen test battery probing reasoning , basic reaction time , numeric memory , visual memory , and prospect i ve memory . Adjusted models included relevant demographic , clinical , and sleep variables . RESULTS Frequent insomnia symptoms were associated with cognitive impairment in unadjusted models ; however , these effects were reversed after full adjustment , leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without . Relative to intermediate chronotype , evening chronotype was associated with superior task performance , while morning chronotype was associated with the poorest performance . Sleep medication use and both long ( > 9 h ) and short ( < 7 h ) sleep duration s were associated with impaired performance . CONCLUSIONS Our results suggest that after adjustment for potential confounding variables , frequent insomnia symptoms may be associated with a small statistical advantage , which is unlikely to be clinical ly meaningful , on simple neurocognitive tasks . Further work is required to examine the mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance and the impairment associated with morning chronotype , sleep medication use , and sleep duration extremes Experimental data indicate a role for the prefrontal cortex in mediating normal sleep physiology , dreaming and sleep-deprivation phenomena . During nonr and om-eye-movement ( NREM ) sleep , frontal cortical activity is characterized by the highest voltage and the slowest brain waves compared to other cortical regions . The differences between the self-awareness experienced in waking and its diminution in dreaming can be explained by deactivation of the dorsolateral prefrontal cortex during REM sleep . Here , we propose that this deactivation results from a direct inhibition of the dorsolateral prefrontal cortical neurons by acetylcholine , the release of which is enhanced during REM sleep . Sleep deprivation influences frontal executive functions in particular , which further emphasizes the sensitivity of the prefrontal cortex to sleep In daily life , we often need to remember to perform an action after , or at , a specific period of time ( e.g. , take pizza out of oven in 15 minutes ) . Surprisingly , little is known about the neural mechanisms that support this form of memory , termed time-based prospect i ve memory ( PM ) . Here we pioneer an fMRI paradigm that enables examination of both sustained and transient processes engaged during time-based PM . Participants were scanned while performing a dem and ing on-going task ( n-back working memory ) , with and without an additional time-based PM dem and . During the PM condition participants could access a hidden clock with a specific button-press response , while in the control condition , pseudo-clocks r and omly appeared and were removed via the same response . Analyses tested for sustained activation associated with the PM condition , and also transient activation associated with clock-checks and the PM target response . Contrary to prior findings with event-based PM ( i.e. , remembering to perform a future action when a specific event occurs ) , no sustained PM-related activity was observed in anterior prefrontal cortex ( aPFC ) or elsewhere in the brain ; instead , transient clock-related activity was observed in this region . Critically , the activation was anticipatory , increasing before clock-check responses . Anticipatory activity prior to the PM target response was weaker in aPFC , but strong in pre-Supplementary Motor Area ( pre-SMA ; relative to clock-check responses ) , suggesting a functional double dissociation related to volitional decision-making . Together , the results suggest that aPFC-activity dynamics during time-based PM reflect a distinct transient monitoring process , enabling integration of the PM intention with current temporal information to facilitate scheduling of upcoming PM-related actions On a daily basis we form numerous intentions to perform specific actions . However , we often have to delay the execution of intended actions while engaging in other dem and ing activities . Previous research has shown that patterns of activity in human prefrontal cortex ( PFC ) can reveal our current intentions . However , two fundamental questions have remained unresolved : ( a ) how does the PFC encode information about future tasks while we are busy engaging in other activities , and ( b ) how does the PFC enable us to commence a stored task at the intended time ? Here we investigate how the brain stores and retrieves future intentions during occupied delays , i.e. while a person is busy performing a different task . For this purpose , we conducted a neuroimaging study with a time-based prospect i ve memory paradigm . Using multivariate pattern classification and fMRI we show that during an occupied delay , activity patterns in the anterior PFC encode the content of ' what ' subjects intend to do next , and ' when ' they intend to do it . Importantly , distinct anterior PFC regions store the ' what ' and ' when ' components of future intentions during occupied maintenance and self-initiated retrieval . These results show a role for anterior PFC activity patterns in storing future action plans and ensuring their timely retrieval STUDY OBJECTIVES To evaluate the effect of sleep deprivation on time-based prospect i ve memory performance , that is , realizing delayed intentions at an appropriate time in the future ( e.g. , to take a medicine in 30 minutes ) . DESIGN Between-subjects experimental design . The experimental group underwent 24 h of total sleep deprivation , and the control group had a regular sleep-wake cycle . Participants were tested at 08:00 . SETTING S Laboratory . PARTICIPANTS Fifty healthy young adults ( mean age 22 ± 2.1 , 31 female ) . INTERVENTIONS 24 h of total sleep deprivation . MEASUREMENTS AND RESULTS Participants were monitored by wrist actigraphy for 3 days before the experimental session . The following cognitive tasks were administered : one time-based prospect i ve memory task and 3 reasoning tasks as ongoing activity . Objective and subjective vigilance was assessed by the psychomotor vigilance task and a visual analog scale , respectively . To measure the time-based prospect i ve memory task we assessed compliance and clock checking behavior ( time monitoring ) . Sleep deprivation negatively affected time-based prospect i ve memory compliance ( P < 0.001 ) , objective vigilance ( mean RT : P < 0.001 ; slowest 10 % RT : P < 0.001 ; lapses : P < 0.005 ) , and subjective vigilance ( P < 0.0001 ) . Performance on reasoning tasks and time monitoring behavior did not differ between groups . CONCLUSIONS The results highlight the potential dangerous effects of total sleep deprivation on human behavior , particularly the ability to perform an intended action after a few minutes . Sleep deprivation strongly compromises time-based prospect i ve memory compliance but does not affect time check frequency . Sleep deprivation may impair the mechanism that allows the integration of information related to time monitoring with the prospect i ve intention Successful realization of planned actions requires the brain to encode intentions over delays . Previous research has indicated that several regions in the rostral or anterior prefrontal cortex ( PFC ) encode delayed intentions . However , different processes may encode the same future task depending on task load during the delay . This difference may depend on the computational re sources available when the delay is occupied with an ongoing task and when it is task-free . Here we directly investigated and compared the representation of delayed intentions in the human brain in the presence and absence of ongoing task load during the delay . We acquired fMRI data in combination with an event-based prospect i ve memory design where human subjects remembered to perform the same future tasks over occupied and task-free delays . We used time-resolved multivoxel pattern classification and found that : ( 1 ) rostrolateral PFC ( BA 46 ) encoded the delayed intention during both delay types ; ( 2 ) rostromedial PFC ( BA 10 ) encoded the intentions during occupied delays ; whereas ( 3 ) a variety of more posterior regions , including the anterior cingulate cortex ( BA 24 ) , the supplementary motor area ( BA 6 ) , and the precuneus , encoded intentions during task-free delays . Overall , the medial PFC encoded delayed intentions more rostrally in the presence of an ongoing delay task and more caudally in its absence . Thus , rostromedial PFC may play a specialized role in the encoding of prospect i ve memory that depends on higher computational dem and s ( e.g. , given higher task load during the delay ) . In contrast , the rostrolateral PFC is a more general area that encodes future intentions regardless of task load Theoretically , prospect i ve memory retrieval can be accomplished either by controlled monitoring of the environment for a target event or by a more reflexive process that spontaneously responds to the presence of a target event . These views were evaluated in Experiments 1 - 4 by examining whether performing a prospect i ve memory task produced costs on the speed of performing the ongoing task . In Experiment 5 , the authors directly tested for the existence of spontaneous retrieval . The results supported the multiprocess theory ( M. A. McDaniel & G. O. Einstein , 2000 ) predictions that ( a ) spontaneous retrieval can occur and can support good prospect i ve memory and ( b ) depending on task dem and s and individual differences , people rely to different degrees on monitoring versus spontaneous retrieval for prospect i ve remembering Several theories of event-based prospect i ve memory were evaluated in 3 experiments . The results depended on the association between the target event and the intended action . For associated target-action pairs ( a ) preexposure of nontargets did not reduce prospect i ve memory , ( b ) divided attention did not reduce prospect i ve memory , ( c ) prospect i ve memory was better than when the target event and intended action were not associated , and ( d ) prospect i ve memory was characterized by retrieval of the precise intended action . These results converge on the view that retrieval is mediated by a reflexive-associative process . In contrast , for unassociated pairs ( a ) preexposure of nontargets reduced prospect i ve memory , and ( b ) divided attention reduced prospect i ve memory . These results implicate cue-focused retrieval processes and are most consistent with a discrepancy-plus- search model . The entire pattern implicates both cue-focused and reflexive-associative processes and more generally supports a multiprocess framework of prospect i ve memory ( M. A. McDaniel & G. O. Einstein , 2000 ) One of the current issues in the field of prospect i ve memory concerns whether having an intention produces a cost to other ongoing activities ( called task interference ) . The evidence to date suggests that certain intentions held over the shorter term do interfere with other tasks . Because the cumulative effect of such costs would be prohibitively expensive in everyday life , the present study examined one means by which that interference may be reduced . Participants who formed a specific association to fulfilling an intention in a future context did not exhibit task interference over the intervening period until that context was encountered . This outcome was observed with both an event-based and a time-based prospect i ve memory task . The results suggest that associating intention fulfillment with a specific context can eliminate task interference , and they emphasize the importance of study ing intentions that are linked to future context s versus those that are not Sleep has been shown to facilitate the consolidation of prospect i ve memory , which is the ability to execute intended actions at the appropriate time in the future . In a previous study , the sleep benefit for prospect i ve memory was mainly expressed as a preservation of prospect i ve memory performance under divided attention as compared to full attention . Based on evidence that intentions are only remembered as long as they have not been executed yet ( cf . ‘ Zeigarnik effect ’ ) , here we asked whether the enhancement of prospect i ve memory by sleep vanishes if the intention is completed before sleep and whether completed intentions can be reinstated to benefit from sleep again . In Experiment 1 , subjects learned cue-associate word pairs in the evening and were prospect ively instructed to detect the cue words and to type in the associates in a lexical decision task ( serving as ongoing task ) 2 h later before a night of sleep or wakefulness . At a second surprise test 2 days later , sleep and wake subjects did not differ in prospect i ve memory performance . Specifically , both sleep and wake groups detected fewer cue words under divided compared to full attention , indicating that sleep does not facilitate the consolidation of completed intentions . Unexpectedly , in Experiment 2 , reinstating the intention , by instructing subjects about the second test after completion of the first test , was not sufficient to restore the sleep benefit . However , in Experiment 3 , where subjects were instructed about both test sessions immediately after learning , sleep facilitated prospect i ve memory performance at the second test after 2 days , evidence d by comparable cue word detection under divided attention and full attention in sleep participants , whereas wake participants detected fewer cue words under divided relative to full attention . Together , these findings show that for prospect i ve memory to benefit from sleep , ( i ) the intention has to be active across the sleep period , and ( ii ) the intention should be induced in temporal proximity to the initial learning session Identifying the processes by which people remember to execute an intention at an appropriate moment ( prospect i ve memory ) remains a fundamental theoretical challenge . According to one account , top-down attentional control is required to maintain activation of the intention , initiate intention retrieval , or support monitoring . A diverging account suggests that bottom-up , spontaneous retrieval can be triggered by cues that have been associated with the intention and that sustained attentional processes are not required . We used a specialized experimental design and functional MRI methods to selectively marshal and identify each process . Results revealed a clear dissociation . One prospect ive-memory task recruited sustained activity in attentional-control areas , such as the anterior prefrontal cortex ; the other engaged purely transient activity in parietal and ventral brain regions associated with attentional capture , target detection , and episodic retrieval . These patterns provide critical evidence that there are two neural routes to prospect i ve memory , with each route emerging under different circumstances Sleep deprivation reduces cognitive performance ; however , its effects on prospect i ve memory ( remembering to perform intended actions ) are unknown . One view suggests that effects of sleep deprivation are limited to tasks associated with prefrontal functioning . An alternative view suggests a global , unspecific effect on human cognition , which should affect a variety of cognitive tasks . We investigated the impact of sleep deprivation ( 25 hours of sleep deprivation vs. no sleep deprivation ) on prospect ive-memory performance in more re source -dem and ing and less re source -dem and ing prospect ive-memory tasks . Performance was lower after sleep deprivation and with a more re source -dem and ing prospect ive-memory task , but these factors did not interact . These results support the view that sleep deprivation affects cognition more globally and demonstrate that sleep deprivation increases failures to carry out intended actions , which may have severe consequences in safety-critical situations Remembering to execute deferred goals ( prospect i ve memory ) is a ubiquitous memory challenge , and one that is often not successfully accomplished . Could sleeping after goal encoding promote later execution ? We evaluated this possibility by instructing participants to execute a prospect i ve memory goal after a short delay ( 20 min ) , a 12-hr wake delay , or a 12-hr sleep delay . Goal execution declined after the 12-hr wake delay relative to the short delay . In contrast , goal execution was relatively preserved after the 12-hr sleep delay relative to the short delay . The sleep-enhanced goal execution was not accompanied by a decline in performance of an ongoing task in which the prospect i ve memory goal was embedded , which suggests that the effect was not a consequence of attentional re sources being reallocated from the ongoing task to the prospect i ve memory goal . Our results suggest that consolidation processes active during sleep increase the probability that a goal will be spontaneously retrieved and executed 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 Abstract Objective : The aim of the present study was to investigate if prospect i ve memory ( PM ) is impaired in idiopathic rapid eye movement ( REM ) sleep behavior disorder ( iRBD ) . RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia . iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein . Method : Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls ( NC ) were enrolled in the present study . Clinical assessment included Movement Disorders Society-Unified Parkinson ’s Disease Rating Scale ( MDS-UPDRS ) , dopamine transporter single-photon emission computed tomography ( DaT-SPECT ) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures . Results : iRBD differed significantly from NC in event-based PM , a number of event-based failures to recall intention and total PM performance ( all p < .001 ) but did not differ in time-based PM and recognition . PM did not contribute to impairment of instrumental activities of daily living in iRBD . Despite being preserved in iRBD in comparison to NC , time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT . Conclusions : We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM . We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses Research on the relationship between habitual sleep patterns and memory performance in older adults is limited . No previous study has used objective and subjective memory measures in a large , older-aged sample to examine the association between sleep and various domains of memory . The aim of this study was to examine the association between objective and subjective measures of sleep with memory performance in older adults , controlling for the effects of potential confounds . One-hundred and seventy-three community-dwelling older adults aged 65 - 89 years in Victoria , Australia completed the study . Objective sleep quality and length were ascertained using the Actiwatch 2 Mini-Mitter , while subjective sleep was measured using the Pittsburgh Sleep Quality Index . Memory was indexed by tests of retrospective memory ( Hopkins Verbal Learning Test - Revised ) , working memory ( n-back , 2-back accuracy ) and prospect i ve memory ( a habitual button pressing task ) . Compared with normative data , overall performance on retrospective memory function was within the average range . Hierarchical regression was used to determine whether objective or subjective measures of sleep predicted memory performances after controlling for demographics , health and mood . After controlling for confounds , actigraphic sleep indices ( greater wake after sleep onset , longer sleep-onset latency and longer total sleep time ) predicted poorer retrospective ( ∆R(2 ) = 0.05 , P = 0.016 ) and working memory ( ∆R(2 ) = 0.05 , P = 0.047 ) . In contrast , subjective sleep indices did not significantly predict memory performances . In community-based older adults , objective ly-measured , habitual sleep indices predict poorer memory performances . It will be important to follow the sample longitudinally to determine trajectories of change over time Prospect i ve memory is memory for the realization of delayed intention . Research ers distinguish 2 kinds of prospect i ve memory : event- and time-based ( G. O. Einstein & M. A. McDaniel , 1990 ) . Taking that distinction into account , the present authors explored participants ' comparative performance under event- and time-based tasks . In an experimental study of 80 participants , the authors investigated the roles of cognitive load and task condition in prospect i ve memory . Cognitive load ( low vs. high ) and task condition ( event- vs. time-based task ) were the independent variables . Accuracy in prospect i ve memory was the dependent variable . Results showed significant differential effects under event- and time-based tasks . However , the effect of cognitive load was more detrimental in time-based prospect i ve memory . Results also revealed that time monitoring is critical in successful performance of time estimation and so in time-based prospect i ve memory . Similarly , participants ' better performance on the event-based prospect i ve memory task showed that they acted on the basis of environment cues . Event-based prospect i ve memory was environmentally cued ; time-based prospect i ve memory required self-initiation Parents of children with special healthcare needs ( CSHCNs ) report poorer sleep than parents of typically developing ( TD ) children , which has been associated with poorer mental health . The relations between sleep disturbances and general health and memory among this population are unknown . The current study aim ed to replicate the findings that parents of CSHCNs report poorer sleep quality than parents of TD children , and further examine how sleep is related to general health and memory . Participants ( 75 parents of TD children ; 97 parents of CSHCNs ) completed an online question naire consisting of : demographics , the Pittsburgh Sleep Quality Index ( PSQI ) , the Prospect i ve Retrospective Memory Question naire ( PRMQ ) and the Healthy Days Measure . Parents of CSHCNs reported worse global sleep than parents of TD children . Parents of CSHCNs took longer to fall asleep at night , had shorter sleep duration and worse subjective sleep quality than parents of TD children . Parents of CSHCNs also had worse prospect i ve memory and were more likely to report poor general health than parents of TD children . Poorer sleep quality was associated with worse memory and health among both parents of TD children and parents of CSHCNs . Results from this study highlight the importance of addressing the sleep of parents of CSHCNs and support the need for more research in this area . By recognizing factors associated with parent 's health and functioning , service providers may be better able to implement support programs for parents of CSHCNs Primary insomnia is characterized by difficulty in falling asleep and /or remaining asleep , by early morning awakening and /or nonrestorative sleep , and result ant daytime dysfunction in the absence of specific physical , mental , or substance-related causes . However , the studies on daytime cognitive functioning of insomnia patients report inconclusive results . This retrospective study aim ed to compare the performance of insomnia patients ( N = 54 ) to that of controls ( N = 113 ) in a naturalistic prospect i ve memory task . Task performance was defined by the percentage of times the event-marker button of an actigraph was pressed , at lights-off time and at wake-up time . The performance pattern in the prospect i ve memory task was similar in both groups . In addition , the task was performed better at lights-off time than at wake-up time regardless of group . Post-hoc subgroup analysis showed that there were more insomnia patients who performed the task perfectly ( i.e. , 100 % ) than controls . Performance at wake-up time was significantly correlated to objective sleep quality ( i.e. , sleep efficiency ) only in insomnia patients We develop a laboratory paradigm for study ing prospect i ve memory and examine whether or not this type of memory is especially difficult for the elderly . In two experiments , young and old subjects were given a prospect i ve memory test ( they were asked to perform an action when a target event occurred ) and three tests of retrospective memory ( short-term memory , free recall , and recognition ) . From the perspective that aging disrupts mainly self-initiated retrieval processes , large age-related decrements in prospect i ve memory were anticipated . However , despite showing reliable age differences on retrospective memory tests , both experiments showed no age deficits in prospect i ve memory . Moreover , regression analyses produced no reliable relation between the prospect i ve and retrospective memory tasks . Also , the experiments showed that external aids and unfamiliar target events benefit prospect i ve memory performance . These results suggest some basic differences between prospect i ve and retrospective memory The magnitude of age differences on event- and time-based prospect i ve memory tasks was investigated in 2 experiments . Participants performed a working memory task and were also required to perform either an event- or time-based prospect i ve action . Control participants performed either the working memory task only or the prospect i ve memory task only . Results yielded age differences on both prospect i ve tasks . The age effect was particularly marked on the time-based task . Performance of the event-based prospect i ve task , however , had a higher cost to performance on the concurrent working memory task than the time-based task did , suggesting that event-based responding has a substantial attentional requirement . The older adults also made a significant number of time-monitoring errors when time monitoring was their sole task . This suggests that some time-based prospect i ve memory deficits in older adults are due to a fundamental deficit in time monitoring rather than to prospect i ve memory The ability to remember to execute delayed intentions is referred to as prospect i ve memory . Previous theoretical and empirical work has focused on isolating whether a particular prospect i ve memory task is supported either by effortful monitoring processes or by cue-driven spontaneous processes . In the present work , we advance the Dynamic Multiprocess Framework , which contends that both monitoring and spontaneous retrieval may be utilized dynamically to support prospect i ve remembering . To capture the dynamic interplay between monitoring and spontaneous retrieval , we had participants perform many ongoing tasks and told them that their prospect i ve memory cue may occur in any context . Following either a 20-min or a 12-h retention interval , the prospect i ve memory cues were presented infrequently across three separate ongoing tasks . The monitoring patterns ( measured as ongoing task cost relative to a between-subjects control condition ) were consistent and robust across the three context s. There was no evidence for monitoring prior to the initial prospect i ve memory cue ; however , individuals who successfully spontaneously retrieved the prospect i ve memory intention , thereby realizing that prospect i ve memory cues could be expected within that context , subsequently monitored . These data support the Dynamic Multiprocess Framework , which contends that individuals will engage monitoring when prospect i ve memory cues are expected , disengage monitoring when cues are not expected , and that when monitoring is disengaged , a probabilistic spontaneous retrieval mechanism can support prospect i ve remembering Abstract Objective : The ability to execute delayed intentions , known as prospect i ve memory ( PM ) , is crucial to everyday living . PM failures are reported in mild cognitive impairment ( MCI ) and Parkinson ’s disease , however , no study to date has investigated PM functioning in individuals at high risk of developing these conditions , precisely those diagnosed with idiopathic REM sleep behavior disorder ( iRBD ) . We aim ed to assess PM in iRBD according to patients ’ cognitive status and to determine the underlying nature of their difficulties . Method : Fifty-eight participants , including 20 healthy controls ( HC ) and 38 polysomnographic-confirmed iRBD patients with ( iRBD-MCI = 13 ) or without ( iRBD-nMCI = 25 ) MCI participated in this study . Following a neuropsychological assessment , PM was evaluated using a self-administered question naire ( PRMQ ) , a simple clinical measure ( envelope test ) , and a laboratory cue salience task . Results : No significant group differences were noted on the PRMQ and envelope test . On the PM laboratory task , non-parametric analyses revealed better detection accuracy in HC than both iRBD groups for all high and low salient cues . While iRBD-nMCI and iRBD-MCI patients performed similarly on the high salient condition , the latter showed significant difficulty in detecting low salient cues . Multiple regression analyses revealed executive dysfunction as the best predictor to significantly account for differences in the low salient condition in iRBD . Conclusion : PM difficulties in iRBD are most important in patients with MCI ( vs without MCI ) and may be attributed to a gradual alteration in executive mechanisms . PM impairment could act as a promising indicator of early cognitive dysfunction in iRBD BACKGROUND Idiopathic rapid eye movement sleep behavior disorder ( iRBD ) likely represents the prodromal stage of synucleinopathy . The present study was to investigate if there was prospect i ve memory ( PM ) impairment and the relationship between different PM tasks and traditional cognitive tests in patients with iRBD . METHODS A total of 28 patients with iRBD , 25 with Parkinson 's disease ( PD ) and 21 healthy controls were included . The Cambridge Prospect i ve Memory Test ( CAMPROMPT ) was used to measure the PM including time-based ( TBPM ) and event-based PM ( EBPM ) . St and ard cognitive tests were administered to all participants . RESULTS EBPM scores were lower only in patients with iRBD , while the obvious PM abnormalities were found in patients with PD . The patients with iRBD and PD performed worse on delayed recall of the Rey Auditory Verbal Learning Test ( RAVLT ) and copy of the Rey-Osterrieth complex figure ( ROCF ) . The EBPM correlated with attention , executive function , and immediate memory besides working memory in patients with iRBD . The PM tasks involved in more memory functions in PD patients . CONCLUSIONS The patients with iRBD were impaired on both episodic memory and EBPM tasks that correlated with attention , executive function , and immediate memory . The PM abnormality was an early cognitive change in iRBD to which more attention should be paid more attention ABSTRACT The high prevalence of sleep disruption among older adults may have implication s for cognitive aging , particularly for higher-order aspects of cognition . One domain where sleep disruption may contribute to age-related deficits is prospect i ve memory — the ability to remember to perform deferred actions at the appropriate time in the future . Community-dwelling older adults ( 55–93 years , N = 133 ) undertook assessment of sleep using actigraphy and participated in a laboratory-based prospect i ve memory task . After controlling for education , sleep disruption ( longer awakenings ) was associated with poorer prospect i ve memory . Additionally , longer awakenings mediated the relationship between older age and poorer prospect i ve memory . Other metrics of sleep disruption , including sleep efficiency and wake after sleep onset , were not related to prospect i ve memory , suggesting that examining the features of individual wake episodes rather than total wake time may help clarify relationships between sleep and cognition . The mediating role of awakening length was partially a function of greater depression and poorer executive function ( shifting ) but not retrospective memory . This study is among the first to examine the association between objective ly measured sleep and prospect i ve memory in older adults . Furthermore , this study is novel in suggesting sleep disruption might contribute to age-related prospect i ve memory deficits ; perhaps , with implication s for cognitive aging more broadly . Our results suggest that there may be opportunities to prevent prospect i ve memory decline by treating sleep problems STUDY OBJECTIVES Previous studies have shown that sleep benefits prospect i ve memory by facilitating spontaneous retrieval processes . Here , we investigated the sleep features supporting such a benefit . METHODS Forty-nine young adults ( mean age ± SD : 22.06 ± 1.71 years ; 18 males ) encoded intentions comprising four related ( phone-unplug earphones ) and four unrelated ( mirror-close the book ) cue-action pairs . They were instructed to remember to perform these actions in response to cue words presented during a semantic categorization task 12 h later . The retention interval involved either a period of wakefulness ( 09:30 - 21:30 ; n = 24 ) or overnight sleep with polysomnographic monitoring ( 21:30 - 09:30 ; n = 25 ) . RESULTS We found a significant Group × Relatedness interaction for prospect i ve memory accuracy ( F = 8.35 , p < 0.01 ) . The sleep group successfully executed a significantly higher percentage of related intentions compared to the wake group ( mean ± st and ard error of the mean ( SEM ) : 94.00 ± 2.61 % vs 66.67 ± 6.84 % , p < 0.001 ) . This benefit for related intentions was associated with longer post-learning slow wave sleep ( r = 0.46 , p < 0.05 ) . In contrast , the percentage of unrelated intentions successfully executed did not differ between groups ( 82.00 ± 5.10 % vs 72.92 ± 6.88 % , p = 0.29 ) . CONCLUSION Slow wave sleep after memory encoding may strengthen the preexisting associations between semantically related cues and actions , thereby facilitating subsequent spontaneous retrieval processes OBJECTIVE Sleep benefits prospect i ve memory in young adults probably in part due to its well-established role in enhancing declarative memory , thereby facilitating retrieval of the intention content . In prior work on adolescents , we did not detect differences in prospect i ve memory comparing five nights of sleep restriction and adequate sleep . Here , we examined whether this might be attributed to a limited role of sleep in benefiting the declarative content in this age group , and whether a sleep benefit on prospect i ve memory would be uncovered with a shorter retention interval . METHODS A total of 59 adolescents ( mean ± st and ard deviation : 16.55 ± 0.94 years ) were instructed to remember to press a special key in response to two target words embedded in a semantic categorization task . Memory was tested after a 12-h retention interval , which included either overnight sleep ( 21:00 - 09:00 , n = 29 ) or daytime wakefulness ( 09:00 - 21:00 , n = 30 ) . RESULTS We found no significant group difference in the percentage of target words correctly responded to ( mean ± st and ard error of the mean for the sleep group : 32.76 ± 6.69 % ; wake group : 41.67 ± 7.61 % , t = 0.88 , p = 0.38 ) . However , participants who slept recalled more target words compared to those who stayed awake ( 98.28 ± 1.72 % vs. 86.67 ± 5.32 % , t = 2.05 , p < 0.05 ) . In addition , a significantly greater proportion of sleep participants ( n = 28 of 29 ) compared to wake participants ( n = 24 of 30 ) recalled both target words correctly ( χ2 = 3.76 , p < 0.05 ) . CONCLUSION These findings suggest that during adolescence , sleep plays a more prominent role in improving memory for the content as compared to the execution of intentions |
450 | 27,327,415 | Low quality evidence suggests that in patients suffering from vertigo from different causes there may be a positive effect of betahistine in terms of reduction in vertigo symptoms .
Betahistine is generally well tolerated with a low risk of adverse events . | BACKGROUND Vertigo is a symptom in which individuals experience a false sensation of movement .
This type of dizziness is thought to originate in the inner ear labyrinth or its neural connections .
It is a commonly experienced symptom and can cause significant problems with carrying out normal activities .
Betahistine is a drug that may work by improving blood flow to the inner ear .
This review examines whether betahistine is more effective than a placebo at treating symptoms of vertigo from different causes .
OBJECTIVES To assess the effects of betahistine in patients with symptoms of vertigo from different causes . | Objective Betahistine is a histamine H1-receptor agonist and H3-receptor antagonist that is administered to treat Menière ’s disease . Despite widespread use , its pharmacological mode of action has not been entirely eluci date d. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinical ly used doses for cochlear microcirculation . Methods Thirty healthy Dunkin-Hartley guinea pigs were r and omly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. ( milligram per kilogram body weight ) , 0.100 mg/kg b. w. , 0.010 mg/kg b. w. , 0.001 mg/kg b. w. in NaCl 0.9 % or NaCl 0.9 % alone as placebo . Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine . Results When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units ( SD : 0.246 ; range : 0.933–1.546 arb . units ) compared to baseline ( p<0.05 ; Two Way Repeated Measures ANOVA/Bonferroni t-test ) . The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9 % had the same effect as placebo . Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages . Conclusions Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries . The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinical ly used single dosages to treat Menière ’s disease . Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière ’s disease might be due to a corresponding increase of cochlear blood flow Thirty-seven patients suffering from vertigo associated with vertebrobasilar insufficiency participated in our prospect i ve , single-center , double-blind , comparative study . Patients were r and omly allocated to treatment with placebo ; betahistine ( 12 mg betahistine dimesylate , one tablet three times daily ) ; or the fixed combination of 20 mg cinnarizine and 40 mg dimenhydrinate ( one tablet three times daily ) for 4 weeks . The primary efficacy end point was the decrease of the mean vertigo score ( S(M ) ) , which was based on the patients ' assessment s of 12 individual vertigo symptoms after 4 weeks of treatment . Patients treated with the fixed combination showed significantly greater reductions of S(M ) as compared to patients receiving placebo ( p < .001 ) or the reference therapy betahistine ( p < .01 ) . The vestibulospinal parameter lateral sway ( Unterberger 's test ) improved to a significantly greater extent in patients taking the fixed combination as compared to those receiving placebo ( p < .001 ) . No serious adverse event was reported in any therapy group . The tolerability of the fixed combination was judged as very good or good by 91 % ( betahistine , 73 % ; placebo , 82 % ) . In conclusion , the fixed combination proved to be statistically more effective than the common antivertiginous drug betahistine in reducing vertebrobasilar insufficiency-associated vertigo symptoms A double-blind , placebo-controlled , clinical study was performed to assess the effects of oral betahistine hydrochloride ( Serc ) on mental impairment and physical disability in patients with established cerebrovascular disease . Fifty-three patients were admitted to the study during 18 months . Forty-five patients completed the study . They received either betahistine 24 mg daily or placebo for eight weeks . Clinical assessment s of general functional activity were done and a battery of nine mental function tests was administered pretreatment and at two-weekly intervals during therapy . The results were analysed statistically using distribution-free tests . Significant differences were demonstrated between betahistine and placebo at week 8 of treatment for associate learning , digit retention , general knowledge , orientation , sentence learning and simple arithmetic . These differences were consistently in favour of betahistine at or close to the 5 % level of significance . The results of the remaining mental function tests showed no significant differences between betahistine and placebo , but trends were in favour of the former . General functional activity assessment s also demonstrated that betahistine-treated patients were significantly better than those on placebo ( P less than or equal to 0.05 ) . No untoward side-effects were noted during the study Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere ’s disease , compared with placebo ? Methods The BEMED trial is a multicentre , double blind , r and omised , placebo controlled , three arm , parallel group , phase III , dose defining superiority trial conducted in 14 German tertiary referral centres ( for neurology or ear , nose , and throat ) . Adults aged 21 - 80 years ( mean age 56 years ) with definite unilateral or bilateral Meniere ’s disease were recruited from March 2008 to November 2012 . Participants received placebo ( n=74 ) , low dose betahistine ( 2 × 24 mg daily , ( n=73 ) ) , or high dose betahistine ( 3 × 48 mg daily , ( n=74 ) ) over nine months . The primary outcome was the number of attacks per 30 days , based on patients ’ diaries during a three month assessment period at months seven to nine . An internet based r and omisation schedule performed a concealed 1:1:1 allocation , stratified by study site . Secondary outcomes included the duration and severity of attacks , change in quality of life scores , and several observer-reported parameters to assess changes in audiological and vestibular function . Study answer and limitations Incidence of attacks related to Meniere ’s disease did not differ between the three treatment groups ( P=0.759 ) . Compared with placebo , attack rate ratios were 1.036 ( 95 % confidence interval 0.942 to 1.140 ) and 1.012 ( 0.919 to 1.114 ) for low dose and high dose betahistine , respectively . The overall monthly attack rate fell significantly by the factor 0.758 ( 0.705 to 0.816 ; P<0.001 ) . The population based , mean monthly incidence averaged over the assessment period was 2.722 ( 1.304 to 6.309 ) , 3.204 ( 1.345 to 7.929 ) , and 3.258 ( 1.685 to 7.266 ) for the placebo , low dose betahistine , and high dose betahistine groups , respectively . Results were consistent for all secondary outcomes . Treatment was well tolerated with no unexpected safety findings . Without a control group of patients who did not receive any intervention to follow the natural course of the disease , the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms . What this study adds Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere ’s disease , compared with placebo . The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere ’s disease . Funding , competing interests , data sharing Support from the German Federal Ministry of Education and Research ( BMBF support code 01KG0708 ) . Potential competing interests have been reported in full at the end of the paper on thebmj.com . Data are available from the corresponding author ( [email protected] ) or biostatistician ( [email protected] ) . Study registration EudraCT no 2005 - 000752 - 32 ; IS RCT N no IS RCT N44359668 A double-blind , placebo-controlled , cross-over clinical trial was performed to assess the effect of betahistine hydrochloride ( Serc ) in Ménière 's disease . The diagnosis was based on paroxysmal attacks of rotational vertigo , with tinnitus , and a fluctuating sensori-neural deafness , together with the results of auditory and vestigular tests . Twenty-eight patients were admitted to the trial over 3 years . Twenty-two patients completed the trial . In total , they received betahistine 32 mg daily , for a period of 16 weeks , and placebo also for the same length of time , preceded in every case by a 4-week pre-treatment period . Daily symptom score cards were kept . There was a statistically significant improvement in favour of the drug with regard to vertigo , tinnitus and deafness . Vertigo was the most responsive symptom . No adverse reactions were observed Objective : The purpose of this study was to determine the prevalence and incidence of vestibular vertigo in the general population and to describe its clinical characteristics and associated factors . Methods : The neurotologic survey had a two-stage general population sampling design : nationwide modified r and om digit dialing sampling for participation in the German National Telephone Health Interview Survey 2003 ( response rate 52 % ) with screening of a r and om sample of 4,869 participants for moderate or severe dizziness or vertigo , followed by detailed neurotologic interviews developed through piloting and validation ( n = 1,003 , response rate 87 % ) . Diagnostic criteria for vestibular vertigo were rotational vertigo , positional vertigo , or recurrent dizziness with nausea and oscillopsia or imbalance . Vestibular vertigo was detected by our interview with a specificity of 94 % and a sensitivity of 88 % in a concurrent validation study using neurotology clinic diagnoses as an accepted st and ard ( n = 61 ) . Results : The lifetime prevalence of vestibular vertigo was 7.8 % , the 1-year prevalence was 5.2 % , and the incidence was 1.5 % . In 80 % of affected individuals , vertigo result ed in a medical consultation , interruption of daily activities , or sick leave . Female sex , age , lower educational level , and various comorbid conditions , including tinnitus , depression , and several cardiovascular diseases and risk factors , were associated with vestibular vertigo in the past year in univariate analysis . In multivariable analysis , only female sex , self-reported depression , tinnitus , hypertension , and dyslipidemia had an independent effect on vestibular vertigo . Conclusions : Vestibular vertigo is common in the general population , affecting more than 5 % of adults in 1 year . The frequency and health care impact of vestibular symptoms at the population level have been underestimated Objective . The purpose of this study is to evaluate the effects of betahistine in addition to Epley maneuver on the quality of life of patients with posterior semicircular canal benign paroxysmal positional vertigo ( BPPV ) of the canalithiasis type . Study Design . Double-blind , r and omized , controlled clinical trial . Setting . Academic university hospital . Subjects and Methods . Seventy-two patients were enrolled in the study . The first group was treated with Epley maneuver only . The second group received placebo drug 2 times daily for 1 week in addition to Epley maneuver , and the third group received 24 mg betahistine 2 times daily for 1 week in addition to Epley maneuver . The effectiveness of the treatments was assessed in each group as well as between them by analyzing and comparing data of 4 different vertigo symptom scales . Results . Epley maneuver , alone or combined with betahistine or placebo , was found to be very effective with a primary success rate of 86.2 % . The symptoms were significantly reduced in group 3 patients overall , and those patients younger or older than 50 years of age who had hypertension , with symptom onset < 1 month , and with attack duration of less than a minute did significantly better with the combination of betahistine 48 mg daily . Conclusion . Betahistine in addition to Epley maneuver is more effective than Epley maneuver alone or combined with placebo with regard to improvement of symptoms in certain patients . However , future clinical studies covering more patients to investigate the benefit of medical treatments in addition to Epley maneuver are needed OBJECTIVE To assess the prevalence of ear , nose and throat ( ENT ) symptoms experienced by individuals living in Scotl and , and their use of GP or hospital services for these problems . METHODS A cross-sectional postal self-completed question naire was sent to a r and om sample of 12,100 households throughout Scotl and . 15,788 individuals aged 14 + years living in the 7244 households who returned the question naire ( adjusted response rate 64.2 % ) participated in the study . RESULTS Roughly a fifth of respondents reported currently having hearing difficulties , including difficulty following conversations when there is background noise and hearing problems causing worry or upset ; few wore a hearing aid regularly . A fifth reported noises in head or ears ( tinnitus ) lasting more than five minutes . In the previous year , between 13 and 18 % of respondents reported persistent nasal symptoms or hayfever , 7 % sneezing or voice problems and 31 % had at least one episode of severe sore throat or tonsillitis . Nearly 21 % of all respondents reported ever having had dizziness in which things seemed to spin around the individual ; 29 % unsteadiness , light-headedness or feeling faint ; 13 % dizziness in which the respondent seemed to move . Important gender , age , occupation and deprivation differences existed in the occurrence of these ENT symptoms . There was considerable variation in the proportion of individuals consulting their GP or being referred to hospital for different problems . CONCLUSIONS ENT problems occur frequently in the community , and most are managed without consulting medical services . Whilst reasonable for many problems , there are likely to be important groups in the community with ENT problems that might benefit from modern interventions Abstract . The present study compares the efficacy and safety of betahistine dihydrochloride to that of a placebo in recurrent vertigo result ing from Meniere 's disease ( MD ) or in paroxysmal positional vertigo ( PPV ) of probable vascular origin . The design was double-blind , multicentre and parallel-group r and omised . Eleven Italian centres enrolled 144 patients : 75 of the patients were treated with betahistine ( 41 MD/34 PPV ) and 69 with placebos ( 40 MD/29 PPV ) . The betahistine dosage was 16 mg twice per day for 3 months . Compared to the placebo , betahistine had a significant effect on the frequency , intensity and duration of vertigo attacks . Associated symptoms and the quality of life also were significantly improved by betahistine . Both the physician 's judgement and the patient 's opinion on the efficacy and acceptability of the treatment were in agreement as to the superiority of betahistine . The effective and safe profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed Vestibular loss induces a combination of postural , oculomotor , and perceptive symptoms that are compensated over time . The aim of this study was to analyze the influence of betahistine dihydrochloride on vestibular compensation . A r and omized , double-blind , placebo-controlled study was performed in Menière 's disease patients who underwent a curative unilateral vestibular neurotomy ( UVN ) . The effects of betahistine treatment were investigated on a broad spectrum of vestibular-induced changes result ing from vestibular loss : body sway , head orientation , ocular cyclotorsion , spontaneous nystagmus , verticality perception , and self-evaluation of the postural stability . The time course of the recovery was compared in 16 patients who received either a placebo or betahistine ( 24 mg b.i.d . ) from 3 days up to 3 months after UVN . Patients were examined before ( day -1 ) and after UVN ( days 7 , 30 , and 90 ) . Results indicate that betahistine reduces the time to recovery by 1 month or more depending on the tested functions . Betahistine was effective as soon as 4 days after treatment administration , and the effect remained during the whole compensation period ( up to 3 months ) . The observed clinical effects may be attributed to an action of betahistine in rebalancing the neuronal activity between contralateral vestibular nuclei A double-blind , cross-over , placebo-controlled study of betahistine dihydrochloride ( 12 mg , t.i.d . ) was carried out in patients with vertigo of peripheral vestibular origin . Twenty-four patients completed the study , which consisted of two six-week treatment periods . The patients were diagnosed as suffering from Menière 's disease ( 15 patients ) , vertigo due to other ( specified ) causes ( five patients ) , or vertigo of unknown origin ( four patients ) . Patients were examined by the investigator at the start of the study and were re-assessed at three-weekly intervals . In addition , they recorded the nature , frequency and severity of their symptoms on diary cards . Both the incidence and severity of dizziness ( the predominant presenting complaint ) were found to be significantly reduced during betahistine treatment ( p = 0.004 ) . The occurrence of nausea and vomiting was also significantly reduced during betahistine treatment ( p = 0.014 and 0.036 respectively ) . There were no statistically significant differences in the results of audiometric or vestibulometric tests , or in the severity of tinnitus or deafness , between the two treatment periods . The overall comparisons of the two periods made by both the patients and the investigator were significantly in favour of betahistine ( p less than 0.001 ) . All diagnostic groups responded favourably to betahistine , confirming the efficacy of betahistine in the symptomatic treatment of peripheral vestibular vertigo . No unwanted signs or symptoms were reported BACKGROUND Dizziness is known to be a common , h and icapping condition in the elderly , and a strong association between dizziness and anxiety disorders has been observed in hospital sample s. However , little is known about the prevalence of dizziness among people of working age in the community and its implication s for psychosocial functioning and general practice consultation and treatment . AIM To determine the prevalence of dizziness , giddiness , vertigo , and unsteadiness , and associations with disability and h and icap , symptoms of panic and agoraphobia , and general practice consultation and treatment . METHOD Postal question naires were completed by 2064 people aged 18 - 64 years r and omly sample d from the patient lists of four London practice s. Vali date d survey items were used to assess symptoms , panic and agoraphobia , levels of occupational disability and h and icap , and general practice consultation and treatment . RESULTS More than one in five responders ( n = 480 ) had experienced dizziness during the past month ; nearly half of these ( n = 225 ) reported some degree of h and icap and 30 % had been dizzy for more than five years . Almost half ( n = 221 ) of those with dizziness also reported anxiety and /or avoidance behaviour . Multiple physical and psychological symptoms were associated with higher levels of h and icap . Only one in four of the 225 dizzy responders reporting some degree of h and icap had received any form of treatment . CONCLUSION Dizziness is a common , chronic , and often untreated symptom in people aged 18 - 65 years , associated with extensive h and icap and psychological morbidity The effects of betahistine hydrochloride ( Serc ) on the clinical features of Ménière 's disease were assessed in two double-blind , placebo-controlled , cross-over clinical studies . The diagnosis was based on a peripheral , fluctuating , recruiting , cochlear ( sensorineural ) deafness in one or both ears , tinnitus ( usually of low tone ) and paroxysmal attacks of rotational vertigo . Appropriate auditory and vestibular analyses confirmed the diagnosis . Twenty-four patients were admitted to the studies after careful screening over two- and -a-half years . Twenty-two patients completed the studies , ten of whom received betahistine and placebo for eight weeks each whereas the remaining twelve were given betahistine and placebo for twelve weeks each . the dose of betahistine was the same ( 16 mg . t.i.d . ) in both studies . Daily symptom score cards kept by all patients throughout the studies showed a statistically significant preference for betahistine over placebo with regard to vertigo ( p = 0 - 025 ) , tinnitus ( p = 0 - 010 ) and fullness of the ear ( p = 0 - 036 ) . Symptom scores of deafness and vomiting indicated trends in favour of betahistine but these did not attain statistical significance . Objective measurements of deafness ( mean db . loss ) , however , showed a highly significant improvement in favour of betahistine , when compared with placebo ( p less than 0 - 001 ) . Vestibular testing revealed no important difference between betahistine and placebo . No unwanted effects or adverse reactions attributable to betahistine were observed during the studies WHEN VERTIGO , associated with Meniere 's syndrome , becomes intractable and incapacitating , the patient becomes a c and i date for surgery . This is not a pleasant outlook for the patient , nor for the treating physician . As a consequence , there has been an incessant but yet unrewarding search for a satisfactory medical treatment . Williams 1 recently reported : Neither the definition , the diagnosis nor the dysfunction of Meniere 's disease is much clearer now than when Meniere first described the condition in 1861 .... On the basis of recently acquired information , we may define Meniere 's disease as a disorder of a predisposed stria vascularis , possibly in response to a hypothalamic stimulus , with the local synthesis of toxic amounts of histamine and possibly of norepinephrine , producing in the stria vascularis the picture of the slow stage of shock , increased hydrodynamic pressure in the endolymphatic system , loss of hearing , and , secondarily , attacks of vertigo , nausea and vomiting . In a Betahistine HCl was studied to evaluate its effect : 1 ) in normal subjects and 2 ) in patients presenting Meniere 's syndrome . The subjective modification of the various symptoms of this syndrome as well as modification of audiometric and vestibular function were studied in 102 patients for periods of up to 4 1/2 years . A double-blind evaluation of ten normal patients with betahistine HCl and a placebo did not show any statistically significant modification of the vestibular response . The subjective evaluation in 102 patients seems to indicate that the drug is more effective in the early stage of the disease . Audio-metric tests frequently demonstrated improvement of hearing in the early stages , but as a rule , this improvement was of a transitory nature . Vestibular function tests , in patients who had no concomitant medication capable of modifying the vestibular response demonstrate a frequent increase of the vestibular response in the early stage of treatment followed by a secondary stage of vestibular response |
451 | 20,408,058 | They used a linguistic analysis method applied to participant-written stories of stress and found that the MBTC group used fewer negative words than the control group over all time points .
Britton and colleagues , in the study : " The Contribution of Mindfulness Practice to a Multicomponent Behavioral Sleep Intervention Following Substance Abuse Treatment in Adolescents , " found that mindfulness practice was associated with improved sleep , psychological health and reduced substance use .
Amaro and colleagues , in their study : " Addiction Treatment Intervention : An Uncontrolled Prospect i ve Pilot Study of Spiritual Self-Schema Therapy with Latina Women , " noted high rates of intervention acceptability , and positive changes in outcomes relevant to HIV prevention and recovery from addiction .
Although conclusive data for mindfulness meditation based interventions as therapies for SUDs are lacking , the preliminary evidence reported in these and prior studies suggests their efficacy .
The promise of mindfulness based therapies is supported by the consistency of positive results demonstrated across different study design s , intervention modalities , subject population s and addictive disorders treated ( 2 ) .
Additional support for the potential efficacy of these interventions in SUDs can be drawn from the results of studies of other clinical conditions ; mindfulness based therapies have been shown effective or potentially effective for a variety of medical and mental health disorders , including stress , anxiety , depression , emotion dysregulation , avoidance coping,(7–12 ) all known risk factors for relapse in SUDs ( 13,14 ) .
In this context , mindfulness meditation based interventions may be particularly helpful for patients with co-occurring substance use and mental health disorders ( " dual diagnosis " ) .
In addition , mindfulness based interventions appear safe , satisfying to clients and may have long-lasting effects in the context of continued meditation practice ( 2,7 ) – all vital qualities of an " ideal " treatment . | In " Psychosocial Treatment for Methamphetamine Use Disorders : a preliminary r and omized controlled trial of cognitive behavior therapy ( CBT ) and acceptance and commitment therapy ( ACT ) , " Smout and colleagues found that , although ACT did not improve treatment outcomes or attendance compared to CBT , it may be a viable therapeutic alternative for methamphetamine use disorders . | Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research Recent studies suggest that months to years of intensive and systematic meditation training can improve attention . However , the lengthy training required has made it difficult to use r and om assignment of participants to conditions to confirm these findings . This article shows that a group r and omly assigned to 5 days of meditation practice with the integrative body – mind training method shows significantly better attention and control of stress than a similarly chosen control group given relaxation training . The training method comes from traditional Chinese medicine and incorporates aspects of other meditation and mindfulness training . Compared with the control group , the experimental group of 40 undergraduate Chinese students given 5 days of 20-min integrative training showed greater improvement in conflict scores on the Attention Network Test , lower anxiety , depression , anger , and fatigue , and higher vigor on the Profile of Mood States scale , a significant decrease in stress-related cortisol , and an increase in immunoreactivity . These results provide a convenient method for study ing the influence of meditation training by using experimental and control methods similar to those used to test drugs or other interventions ABSTRACT Stress is important in substance use disorders ( SUDs ) . Mindfulness training ( MT ) has shown promise for stress-related maladies . No studies have compared MT to empirically vali date d treatments for SUDs . The goals of this study were to assess MT compared to cognitive behavioral therapy ( CBT ) in substance use and treatment acceptability , and specificity of MT compared to CBT in targeting stress reactivity . Thirty-six individuals with alcohol and /or cocaine use disorders were r and omly assigned to receive group MT or CBT in an outpatient setting . Drug use was assessed weekly . After treatment , responses to personalized stress provocation were measured . Fourteen individuals completed treatment . There were no differences in treatment satisfaction or drug use between groups . The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT . This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress BACKGROUND Research has shown that exposure to stress/negative affect and to alcohol cues can each increase alcohol craving and relapse susceptibility in alcohol-dependent individuals . However , whether the emotional and physiological states associated with stress-induced and alcohol cue-induced craving are comparable has not been well studied . Therefore , this study examined the craving , emotional , and physiological responses to stress and to alcohol cues in treatment-engaged , 4-week abstinent , alcohol-dependent individuals using analogous stress and alcohol cue imagery methods . METHOD Twenty treatment-seeking , alcohol-dependent participants ( 18 males/2 females ) were exposed to a brief 5-minute guided imagery procedure that involved imagining a recent personal stressful situation , a personal alcohol cue-related situation , and a neutral-relaxing situation , 1 imagery per session presented in r and om order . Alcohol craving , anxiety and emotion rating scales , cardiovascular measures , and salivary cortisol were compared across the 3 conditions . RESULTS Exposure to stress and to alcohol cues each produced significant increases in alcohol craving , anxiety , and negative emotions and decreases in positive emotions . Stress-induced alcohol craving was significantly correlated with increases in sadness , anger , and anxiety ratings , but alcohol cue-induced craving was associated with decreases in positive affect ( joy and neutral relaxed state ) and increases in anxiety and fear ratings . Furthermore , stress increased systolic and diastolic blood pressure responses , but significant increases in salivary cortisol were only observed in the alcohol cue condition . CONCLUSIONS Although both stress and alcohol cues produce increases in anxiety associated with alcohol craving , each produced a dissociable psychobiological state involving subjective emotional , cardiovascular , and cortisol responses . These data could have significant implication s for underst and ing the specific psychobiology associated with stress or alcohol cue exposure and their potential effects on alcohol relapse susceptibility ABSTRACT The current study is the first r and omized-controlled trial evaluating the feasibility and initial efficacy of an 8-week outpatient Mindfulness-Based Relapse Prevention ( MBRP ) program as compared to treatment as usual ( TAU ) . Participants were 168 adults with substance use disorders who had recently completed intensive inpatient or outpatient treatment . Assessment s were administered pre-intervention , post-intervention , and 2 and 4 months post-intervention . Feasibility of MBRP was demonstrated by consistent homework compliance , attendance , and participant satisfaction . Initial efficacy was supported by significantly lower rates of substance use in those who received MBRP as compared to those in TAU over the 4-month post-intervention period . Additionally , MBRP participants demonstrated greater decreases in craving , and increases in acceptance and acting with awareness as compared to TAU . Results from this initial trial support the feasibility and initial efficacy of MBRP as an aftercare approach for individuals who have recently completed an intensive treatment for substance use disorders |
452 | 25,312,767 | The 45 ° flexion PA view showed a higher sensitivity than the st and ing AP view for detecting severe arthritis involving either the medial or lateral tibiofemoral compartment .
There was no difference in the specificities for the 2 views .
The direct comparison of the Kellgren-Lawrence and the JSN radiographic grading systems found no clinical difference between the 2 systems regarding the sensitivities , although the specificity was greater for the JSN system .
However , as an inexpensive screening tool , the 45 ° flexion PA view is more sensitive than the st and ing AP view to detect severe tibiofemoral osteoarthritis .
When evaluating the radiograph for severe osteoarthritis using either the Kellgren-Lawrence or JSN grading system , there is no clinical difference in the sensitivity between the 2 methods ; however , the JSN may be more specific for ruling in severe osteoarthritis in the medial compartment . | PURPOSE The purpose of this study was to perform a systematic review of the available literature to define the level of quality evidence for determining the sensitivity and specificity of different radiographic views in detecting knee osteoarthritis and to determine the impact of different grading systems on the ability to detect knee osteoarthritis .
CONCLUSIONS The ability to detect knee osteoarthritis continues to be difficult without using advanced imaging . | Objective : To assess the clinical relevance of mean and minimum femorotibial joint space narrowing ( JSN ) for predicting future osteoarthritis related surgery in patients with knee osteoarthritis . Methods : 126 subjects with primary knee osteoarthritis were followed prospect ively for a mean eight years . Minimum and mean joint space width ( JSW ) were assessed from st and ard x rays at baseline and after a follow up of three years . The rate of knee osteoarthritis related surgery was recorded for the following five years . Results : After a mean follow up of eight years , 16 patients ( 12.7 % ) had received osteoarthritis related joint surgery . The areas under the curves ( AUC ) result ing from the receiver operating characteristic curve analyses for predicting osteoarthritis surgery were 0.73 ( p = 0.006 ) for minimum JSN and 0.55 ( p = 0.54 ) for mean JSN . The cut off for minimum JSN maximising sensitivity and specificity for predicting future surgery was a change of 0.7 mm or more in minimum joint space width over a period of three years . However , no meaningful differences were observed for cut off values between 0.5 and 0.8 mm The relative risk ( adjusted for age , body mass index , baseline symptoms , and baseline JSW ) of experiencing osteoarthritis related surgery during the eight year of follow up was 5.15 ( 95 % confidence interval , 1.70 to 15.60 ) ( p = 0.004 ) in patients with a minimum joint space narrowing of 0.7 mm or more during the first three years of the study . Conclusions : A cut off of 0.5 to 0.8 mm in minimum JSN , measured on st and ard x rays , reflects a clinical ly relevant progression in patients with knee osteoarthritis OBJECTIVE The failure to image the patellofemoral joint or the posterior knee compartment when evaluating persons for knee osteoarthritis may result in missed cases . While the skyline view has been recommended due to more reproducible assessment of the patellofemoral joint space , the lateral view may be easier to acquire and provides different information . We evaluated the sensitivity of different combinations of X-ray views ( anteroposterior and lateral ; anteroposterior and skyline ; all three views ) in 377 persons with knee symptoms who had all three views available and had a definite osteophyte on at least one view . RESULTS Of the different views , skylines had to be excluded most often because the image of the patellofemoral joint was technically unsatisfactory . In the remaining knees , adding either a lateral or a skyline view to an anteroposterior view yielded roughly equal and high sensitivity ( 94 - 97 % ) when compared with the gold st and ard of a positive X-ray on any of the three views . CONCLUSION As long as at least an anteroposterior view and one image of the patellofemoral joint is obtained ( either skyline or lateral ) , few cases with radiographic disease will be missed . For clinical or epidemiological studies the lateral view may be easier to acquire with high quality than the skyline view OBJECTIVE Flexion and erect st and ing radiographs were evaluated in the current study to compare their sensitivity in detecting articular cartilage wear . DESIGN Prospect i ve cohort study . SETTING A tertiary care hospital outpatient orthopedic clinic . PATIENTS All patients with osteoarthritis of the knee ages 40 to 75 scheduled for arthroscopic debridement between March 1995 and November 1997 were considered for the current study . INTERVENTION Radiographs were obtained 1 week preoperatively in both the 3-foot st and ing anteroposterior ( AP ) and a 45 degrees posteroanterior ( PA ) flexion weight-bearing projection . Joint space height was measured with a ruler in millimeters at the narrowest point of each compartment . All radiographs were assessed by two independent observers who were blinded to the arthroscopic findings and clinical symptoms of the subjects . MAIN OUTCOME MEASURES Prediction accuracy of each radiograph for severe Grade IV articular cartilage wear in tibio-femoral compartments . RESULTS One hundred fifty-two patients with a mean ( + /- SD ) age of 60.5+/-8.5 years were enrolled in the study . Fifty-one percent were female . Twelve patients were categorized as having severe lateral compartment articular chondropathy ( Grade IV ) at the time of arthroscopy . The lateral joint space height averaged 1.0+/-1.7 mm SD on the 45 degrees PA radiograph compared with 2.7+/-1.1 mm SD on the 3-foot st and ing AP view . Using a cutoff of 2 mm or less , the 45 degrees PA view was much more sensitive ( 83 % versus 42 % ) at correctly detecting the most severe chondropathy . Forty-one patients were classified with severe Grade IV medial compartment chondropathy at arthroscopy . There was little difference in the average joint space height measured by the 45 degrees PA view ( 1.4+/-1.4 mm SD ) or the 3-foot st and ing AP view ( 1.9+/-1.6 mm SD ) . A number of cutoff measures were evaluated , but no significant advantage could be found for either view in evaluating the medial compartment severity . CONCLUSIONS The bilateral 45 degrees PA is superior for detecting lateral compartment wear but offers no advantage on the medial side . This view should be considered as the screening radiograph of choice in evaluating osteoarthritis of the knee OBJECTIVE To compare quantitative estimates of change in joint space width ( JSW ) with semiquantitative ratings of the progression of joint space narrowing ( JSN ) with respect to sensitivity to change over time . METHODS 431 obese women 45 to 64 years old with unilateral radiographic knee osteoarthritis were r and omised to 30 months ' treatment with doxycycline 100 mg twice daily or placebo . Quantitative estimates of change in JSW in the medial tibiofemoral compartment from fluoroscopically assisted semiflexed AP radiographs were obtained at baseline and 16 and 30 months after r and omisation . Radiographic JSN was rated ( 0 - 3 scale ) in the same images by two readers using a st and ard atlas . Changes in overall severity of knee osteoarthritis were derived from gradings of conventional st and ing AP radiographs at baseline and 30 months , with blinding to treatment group and chronological order of examination . RESULTS Follow up radiographs were obtained from 381 subjects ( 88 % ) at 16 months and from 367 ( 85 % ) at 30 months . The treatment groups did not differ in the frequency of significant loss of JSW by dichotomous criteria ( > or = 0.5 mm , > or = 1.0 mm , > or = 20 % , or > or = 50 % of baseline JSW ) . Progressors and non-progressors , as defined by each of the dichotomous outcomes , differed significantly in mean value for quantitative measurement of change in JSW at 30 months ( p < or = 0.001 ) . CONCLUSIONS Quantitative and semiquantitative indicators of progression of osteoarthritis in fluoroscopically st and ardised radiographs of osteoarthritic knees are highly related , but the effect of doxycycline on articular cartilage thickness was more easily detected with quantitative measurements of change in JSW than with semiquantitative ratings of JSN OBJECTIVE To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis ( OA ) over a 3-year period . METHODS A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years . Fractal signature analysis ( FSA ) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees , using a commercially available software tool . OA progression was defined as a change in joint space narrowing ( JSN ) or osteophyte formation of 1 grade according to a st and ardized knee atlas . Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius . RESULTS Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression ( area under the curve [ AUC ] 0.75 , of a receiver operating characteristic curve ) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment . Traditional covariates ( age , sex , body mass index , knee pain ) , general bone mineral content , and joint space width at baseline were no more effective than r and om variables for predicting OA progression ( AUC 0.52 - 0.58 ) . The predictive model with maximum effectiveness combined fractal signature at baseline , knee alignment , traditional covariates , and bone mineral content ( AUC 0.79 ) . CONCLUSION We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA . Although the method needs to be vali date d in a second cohort , our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression Preoperatively predicting chondral damage is important . Weightbearing radiographs , including the st and ing antero- posterior and 45 ° flexion posteroanterior views traditionally have been used for this purpose . We wanted to determine if one radiograph had superior sensitivity or specificity in detecting arthroscopically confirmed Grade II chondromalacia ( mild arthritis ) . A st and ard prospect i ve st and ing radio- graphic protocol was design ed for all patients who presented to a sports medicine center with knee complaints . Patients who had subsequent arthroscopic surgery had their radio- graphs measured in a blinded manner for articular cartilage intervals in millimeters to detect joint-space narrowing . Intraarticular chondral damage was correlated with the radio- graphic findings . Three hundred forty-nine of a possible 411 ( 87 % ) patients during a 2-year period had both radiographs and subsequent arthroscopic grading of chondromalacia . This has been the largest study that correlated arthroscopic chondromalacia grade s with two commonly preferred weightbearing radiograph projections . Despite specificities greater than 90 % , the sensitivity was extremely low and neither st and ing radiograph was superior . Neither radiograph was useful in detecting Grade II chondral damage . Level of Evidence : Diagnostic study , Level I-1 ( testing of previously developed diagnostic criteria in series of consecutive patients -with universally applied reference “ gold ” st and ard ) . See the Guidelines for Authors for a complete description of levels of evidence We proposed to establish a system of assessing severity of chondropathy taking into account localization , size , and depth of cartilage lesions . The design of the study was prospect i ve and multicenter . The subjects were 755 patients who had undergone arthroscopy of the knee . Criteria for assessment of severity of chondropathy were as follows : ( a ) Physician 's overall assessment using a 100-mm-long Visual Analogue Scale , and ( b ) size , grade , and localization of cartilage lesions recorded on a diagram . We used multivariate parametric and nonparametric analyses . The analyses result ed in two systems of assessing severity of chondropathy : SFA scoring for the three compartments of the knee , which is a continuous variable , and SFA grading , which is a semiquantitative variable . These systems seem to be of clinical relevance . However , more studies are required to further vali date them and their capacity to detect changes in severity of chondropathy Twenty-seven patients with chronic knee pain were examined prospect ively using conventional radiography , radionuclide angiography , planar bone scintigraphy , and single-photon emission computed tomographic ( SPECT ) bone scintigraphy . When the results of subsequent arthroscopic examination of all three compartments of the knee were correlated with those of the noninvasive methods , SPECT bone scintigraphy was found to be most sensitive for evaluating the extent of osteoarthritis . Differences in detection sensitivity for articular cartilage damage and synovitis were greatest in the patellofemoral compartment . The frequency with which hyperemia was present in association with cartilage damage and synovitis indicates that osteoarthritis of the knee is capable of producing hyperemia and further implies that increased perfusion can not be used to distinguish with confidence between osteoarthritis and septic processes involving the knee . SPECT ( 1.00 ) and planar ( 0.91 ) bone scintigraphy were highly sensitive indicators of torn menisci in a subgroup of 14 patients , each having a prearthroscopic clinical diagnosis of a torn meniscus . This result suggests that for patients with chronic knee pain and clinical suggestion of a torn meniscus , bone scintigraphy has significant potential as a high-sensitivity , prearthroscopic screening examination OBJECTIVE To evaluate progression of joint space narrowing in radiographs of osteoarthritic ( OA ) knees imaged in both the st and ing anteroposterior ( AP ) and the Lyon schuss positions , using alternative methods to measure joint space width ( JSW ) . METHODS St and ing AP ( extended view ) and Lyon schuss ( posteroanterior [ PA ] view , with 20 - 30 degrees of flexion ) radiographic images of 58 OA knees were obtained twice ( at baseline and 2 years later ) . With both methods , fluoroscopy was used to align the anterior and posterior margins of the medial or lateral tibial plateau with the central x-ray beam . Minimum JSW , mean JSW , and joint space area ( JSA ) of the medial or lateral femorotibial joint space were measured using a new digital image analysis system . The effects of knee flexion versus extension and parallel versus nonparallel tibial plateau alignment were evaluated with respect to the reproducibility of JSW in repeated examinations ( intraclass correlation coefficient [ ICC ] ) , the mean of within-knee st and ard deviations of repeated measurements ( SD(m ) ) , and the sensitivity to changes in JSW in serial radiographs ( st and ardized response mean [ SRM ] ) . RESULTS The performance of the new software , as assessed by the reproducibility of repeated measurements of minimum JSW on the same image , was excellent in both the st and ing AP ( ICC = 0.98 ) and Lyon schuss radiographs ( 2 SD(m ) = 0.5 mm , ICC = 0.98 ) . The reproducibility in different radiographs of the same knee was not evaluated . However , over 2 years , the mean ( + /- SD ) decrease in the minimum JSW of OA knees was 0.17 + /- 0.75 mm in st and ing AP radiographs ( P not significant ) and 0.24 + /- 0.50 mm in Lyon schuss views ( P = 0.007 ) , with SRMs of 0.23 and 0.48 , respectively . The quality of alignment of the tibial plateau was satisfactory ( < 1 mm between anterior and posterior margins of the medial tibial plateau ) in 66 % of the pairs of Lyon schuss radiographs and in 57 % of the pairs of st and ing AP radiographs . In the Lyon schuss radiographs , SRM was highly dependent on tibial plateau alignment . Minimum JSW was more sensitive to change than was mean JSW or JSA , in paired Lyon schuss radiographs that exhibited satisfactory alignment . CONCLUSION Compared with the st and ing AP radiograph , PA imaging of the knee in 20 - 30 degrees flexion ( the schuss position ) increases the reproducibility of radiographic JSW measurements in OA knees and the sensitivity to change in JSW in serial radiographs . Sensitivity to change in minimum JSW is notably increased by aligning the medial tibial plateau with the central x-ray beam in the Lyon schuss radiograph Objective : The objectives of this study are to design and evaluate a CT-free intra-operative planning and navigation system for high tibial opening wedge osteotomy . This is a widely accepted treatment for medial compartment osteoarthritis and other lower extremity deformities , particularly in young and active patients for whom total knee replacement is not advised . However , it is a technically dem and ing procedure . Conventional preoperative planning and surgical techniques have so far been inaccurate , and often result ing in postoperative malalignment representing either under- or over-correction , which is the main reason for poor long-term results . In addition , conventional techniques have the potential to damage the lateral hinge cortex and tibial neurovascular structures , which may cause fixation failure , loss of correction , or peroneal nerve paralysis . All these common problems can be addressed by the use of a surgical navigation system . Material s and Methods : Surgical instruments are tracked optically with the SurgiGATE ® navigation system ( PRAXIM MediVision , La Tronche , France ) . Following exposure , dynamical reference bases are attached to the femur , tibia , and proximal fragment of the tibia . A patient-specific coordinate system is then established , on the basis of registered anatomical l and marks . After intra-operative deformity measurement and correction planning , the osteotomy is performed under navigational guidance . The deformities are corrected by realigning the mechanical axis of the affected limb from the diseased medial compartment to the healthy lateral side . The wedge size , joint line orientation , and tibial plateau slope are monitored during correction . Besides correcting uni-planar varus deformities , the system provides the functionality to correct complex multi-planar deformities with a single cut . Furthermore , with on-the-fly visualization of surgical instruments on multiple fluoroscopic images , penetration of the hinge cortex and damage to the neurovascular structures due to an inappropriate osteotomy can be avoided . Results : The laboratory evaluation with a plastic bone model ( Synbone AG , Davos , Switzerl and ) shows that the error of deformity correction is < 1.7 ° ( 95 % confidence interval ) in the frontal plane and < 2.3 ° ( 95 % confidence interval ) in the sagittal plane . The preliminary clinical trial confirms these results . Conclusion : A novel CT-free navigation system for high tibial osteotomy has been developed and evaluated , which holds the promise of improved accuracy , reliability , and safety of this procedure The purpose of this paper is to describe automated techniques for the visualization and mapping of articular cartilage in magnetic resonance ( MR ) images of the osteoarthritic knee . The MR sequences and analysis software which will be described allow the assessment of cartilage damage using a range of st and ard scanners . With high field strength systems it would be possible , using these techniques , to assess micro-damage . The specific aim of the paper is to develop and vali date software for automated segmentation and thickness mapping of articular cartilage from three-dimensional ( 3-D ) gradient-echo MR images of the knee . The method can also be used for MR-based assessment of tissue engineered grafts . Typical values of cartilage thickness over seven defined regions can be obtained in patients with osteoarthritis ( OA ) and control subjects without OA . Three groups of patients were studied . The first group comprised patients with moderate OA in the age range 45 - 73 years . The second group comprised asymptomatic volunteers of 50 - 65 years ; the third group , younger volunteers selected by clinical interview , history and X-ray . In this paper , sagittal 3-D spoiled-gradient steady-state acquisition images were obtained using a 1.5-T GE whole-body scanner with a specialist knee coil . For validation bovine and porcine cadaveric knees were given artificial cartilage lesions and then imaged . The animal validations showed close agreement between direct lesion measurements and those obtained from the MR images . The feasibility of semi-automated segmentation is demonstrated . Regional cartilage thickness values are seen as having practical application for fully automated detection of OA lesions even down to the su bmi crometer level OBJECTIVE : To compare two plain radiographic methods for sensitivity to detect progression of patellofemoral osteoarthritis . METHODS : Two sets of paired skyline and lateral knee radiographs from 54 hospital referred patients ( 108 knees ) with knee osteoarthritis were taken an average of 31 months apart ( range 12 - 40 ) . Films were examined separately in r and om order by a single observer blind to patient identity and time order . Minimum joint space was measured by metered caliper ; individual features of osteoarthritis were grade d 0 - 3 using an atlas . RESULTS : Intraobserver reproducibility assessed on 40 knees was to within + /- 0.5 mm for skyline lateral facet and + /- 0.7 mm for medial facet and lateral views . On the lateral view measured joint space decreased in 51 % of knees but increased in 43 % , with overall no significant mean group change with time ( -0.2 mm , 95 % confidence interval , 0.1 to -0.5 ) . By contrast on the skyline view joint space decreased in at least one facet in 71 % of knees , with significant decrease in mean joint space for both lateral facets ( -0.4 mm , 95 % CI , -0.2 to -0.6 ) and medial facets ( -0.5 mm , 95 % CI , -0.1 to -0.8 ) . CONCLUSIONS : It is possible to detect significant joint space loss with time on the skyline view that is not apparent on the lateral view . The skyline view should be the method of choice to detect progression of patellofemoral osteoarthritis OBJECTIVE Quantitative evaluation of radiographic methods proposed to improve the detection of joint space narrowing ( JSN ) in femorotibial osteoarthritis ( OA ) . METHODS Thirty-two consecutive patients with knee OA and five normal controls had three different weight-bearing radiographs of the knee : ( 1 ) anteroposterior film of both knees in full extension ( extended knees ) , ( 2 ) anteroposterior film of one knee in extension while the patient was st and ing on the homolateral foot ( st and ing on homolateral foot ) , ( 3 ) posteroanterior film of both knees flexed at 30 degrees ( schuss view ) . Joint space was analyzed blind using both an evaluation of JSN with a six- grade scale ( JSN score ) and an image analyser computer measurement of the mean joint space width ( mean JSW ) . The medial compartment of medial femorotibial OA knees , the lateral compartment of lateral femorotibial OA knees , as well as both compartments of control knees , were measured . Extended knee and schuss views were made 1 year later in 10 patients for the evaluation of sensitivity to change . RESULTS The JSN scores + /- S.D. in schuss , st and ing on the homolateral foot and extended knee views were 2.75 + /- 1.31 , 1.95 + /- 1.3 and 1.66 + /- 1.27 , respectively . The mean JSW + /- S.D. in schuss , st and ing on the homolateral foot , and extended knee views were 2.9 + /- 1.9 mm , 3.5 + /- 1.6 mm and 3.8 + /- 1.5 mm , respectively . Changes in JSN scores and mean JSW with schuss view increased with OA severity . In controls , JSW of the medial compartment did not vary in the three views . JSW of the lateral compartment of controls was significantly larger in the schuss view . The change in JSW after 1 year was -0.41 mm ( P = 0.02 ) in the schuss view and -0.17 mm ( P > 0.05 ) in the extended knee view . CONCLUSION The schuss view is suggested as the most accurate method for the evaluation of JSW in femorotibial OA Background : The available evidence supporting the use of arthroscopic débridement for the treatment of symptomatic osteoarthritis of the knee is largely retrospective and lacks vali date d health-related quality -of-life measures . The goal of the study was to prospect ively assess a cohort of patients with osteoarthritis of the knee who were selected for arthroscopic débridement and determine which clinical criteria favor a sustained improvement in health-related quality of life after two years of follow-up . Methods : One hundred and twenty-six patients with symptomatic primary osteoarthritis of the knee underwent arthroscopic débridement of the knee after failure of medical management . Two groups of surgeons ( postgraduate fellows and attending staff ) independently evaluated the patients preoperatively with use of a st and ardized assessment of clinical symptoms and signs and plain radiography . The intervention was arthroscopic débridement , which included resection of unstable chondral flaps and meniscal tears . Abrasion was not performed . Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , a disease-specific scale , and the Short Form-36 ( SF-36 ) , a generic outcome measure . Results : Sixty-seven ( 53 % ) of the 126 patients were female , and the mean age ( and st and ard deviation ) was 61.7 ± 8.6 years ( range , forty-three to seventy-five years ) . The medial compartment was more frequently and severely involved , with 57 % showing Grade -III or IV involvement , according to the system of Dougados et al. Seventy-nine patients ( 63 % ) had an unstable meniscal tear . Fifty-six patients ( 44 % ) were rated as having had a clinical ly important reduction in pain , as determined with the WOMAC pain scale , at two years after the arthroscopic débridement . Physicians were poor at predicting which patients would have improvement . The rate of accuracy of the fellows and staff was 54 % and 59 % , respectively , and their agreement was only slightly better than chance , with a kappa of 0.27 ( 95 % confidence interval , 0.09 to 0.45 ) . Only three variables were significantly associated with improvement : the presence of medial joint-line tenderness ( p = 0.04 ) , a positive Steinman test ( p = 0.01 ) , and the presence of an unstable meniscal tear at arthroscopy ( p = 0.01 ) . Conclusions : The prospect ively evaluated quality -of-life benefit from arthroscopic débridement of the osteoarthritic knee is less than that reported in previous retrospective surveys on satisfaction . These results may serve as a baseline for comparison against more sophisticated procedures for resurfacing of the articular cartilage . Clinical variables were only partially helpful for predicting a successful result after arthroscopic débridement , and a search for other biologic markers ( such as synovial fluid ) may be of benefit . Level of Evidence : Therapeutic study , Level IV ( case series [ no , or historical , control group ] ) . See p. 2 for complete description of levels of evidence OBJECTIVE The hallmark of osteoarthritis ( OA ) is the loss of articular cartilage . This loss arises from an imbalance between cartilage synthesis and cartilage degradation over a variable period of time . The aims of this study were to investigate the rates of these processes in patients with knee OA using two new molecular markers and to investigate whether the combined use of these markers could predict the progression of joint damage evaluated by both radiography and arthroscopy of the joints during a period of 1 year . METHODS Seventy-five patients with medial knee OA ( 51 women , 24 men ; mean + /- SD age 63 + /- 8 years , mean + /- SD disease duration 4.8 + /- 5.2 years ) were studied prospect ively . At baseline , we measured serum levels of N-propeptide of type IIA procollagen ( PIIANP ) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen ( CTX-II ) as markers of type II collagen synthesis and degradation , respectively . Joint space width ( JSW ) on radiography and medial chondropathy at arthroscopy ( assessed using a 100-mm visual analog scale [ VAS ] ) were measured in all patients at baseline and in 52 patients at 1 year . Progression of joint destruction was defined as a decrease of > or = 0.5 mm in JSW on radiography and as increased chondropathy ( an increase in the VAS score of > 8.0 units ) between the baseline and 1-year evaluations . RESULTS At baseline , compared with 58 healthy age- and sex-matched controls , patients with knee OA had decreased serum levels of PIIANP ( 20 ng/ml versus 29 ng/ml ; P < 0.001 ) and increased urinary excretion of CTX-II ( 618 ng/mmole creatinine [ Cr ] versus 367 ng/mmole Cr ; P < 0.001 ) . The highest discrimination between OA patients and controls was obtained by combining PIIANP and CTX-II in an uncoupling index ( Z score CTX-II - Z score PIIANP ) , which yielded a mean Z score of 2.9 ( P < 0.0001 ) . Increased baseline values in the uncoupling index were associated with greater progression of joint damage evaluated either by changes in JSW ( r = -0.46 , P = 0.0016 ) or by VAS score ( r = 0.36 , P = 0.014 ) . Patients with both low levels of PIIANP ( less than or equal to the mean - 1 SD in controls ) and high levels of CTX-II ( greater than or equal to the mean + 1 SD in controls ) had an 8-fold more rapid progression of joint damage than other patients ( P = 0.012 and P < 0.0001 as assessed by radiography and arthroscopy , respectively ) and had relative risks of progression of 2.9 ( 95 % confidence interval [ 95 % CI ] 0.80 - 11.1 ) and 9.3 ( 95 % CI 2.2 - 39 ) by radiography and arthroscopy , respectively . CONCLUSION Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II . The combination of these two new markers could be useful for identifying knee OA patients at high risk for rapid progression of joint damage 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 . |
453 | 32,259,696 | Associations between HCRT1 , metabolic and reproductive function are inconsistent . | The hypocretin system consists of two peptides hypocretin-1 and hypocretin-2 ( HCRT1 and HCRT2 ) .
Hypocretin-containing neurons are located in the posterior and lateral hypothalamus , and have widespread projections throughout the brain and spinal cord .
In addition to its presence in the cerebrospinal fluid ( CSF ) , peripheral HCRT1 has been detected in plasma .
Robust experimental evidence demonstrates functions of hypothalamic-originated HCRT1 in regulation of multiple biological systems related to sleep-wake states , energy homeostasis and endocrine function .
In contrast , HCRT1 studies with human participants are limited by the necessarily invasive assessment of CSF HCRT1 to patients with underlying morbidity . | Purpose To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17β-estradiol plus drospirenone . Methods Twenty postmenopausal and 20 premenopausal women were enrolled in a prospect i ve comparative study . Postmenopausal women received 1 mg 17β-estradiol plus 2 mg drospirenone daily for 6 months . Measurements of body mass index ( BMI ) , waist/hip ratio and plasmatic levels of insulin , glucose , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , triglyceride , leptin , adiponectin , orexin-A , glucagon-like peptide-1 ( GLP-1 ) and ghrelin were performed in premenopausal ( group 1 ) and postmenopausal women and in the latter before ( group 2a ) and after ( group 2b ) 6 months treatment with 17β-estradiol plus drospirenone . Results No significant changes in BMI s , insulin and glucose were observed between group 1 and 2a ; and group 2a and 2b . GLP-1 levels were significantly increased in group 1 compared to group 2a ( p = 0.035 ) . Leptin levels were significantly increased ( p = 0.001 ) and GLP-1 levels were significantly decreased ( p = 0.021 ) in group 2b compared to group 2a . HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1 . ( p = 0.030 , p = 0.001 , p = 0.020 ; respectively ) LDL was significantly decreased ( p = 0.010 ) in group 2b compared to group 2a . GLP-1 had a positive correlation with orexin-A ( p < 0.001 , r = 0.520 ) and negative correlation with leptin ( p = 0.008 , r = −0.345 ) . Conclusion Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17β-estradiol plus drospirenone treatment . GLP-1 levels were significantly lower after the menopause compared to premenopausal levels . Orexin-A and GLP-1 were positively correlated Hypocretin ( orexin ) peptides are involved in the regulation of energy balance and pituitary hormone release . Narcolepsy is a sleep disorder characterized by disruption of hypocretin neurotransmission . Pituitary LH secretion is diminished in hypocretin-deficient animal models , and intracerebroventricular administration of hypocretin-1 activates the hypothalamo-pituitary-gonadal axis in rats . We evaluated whether hypocretin deficiency affects gonadotropin release in humans . To this end , we deconvolved 24-h serum concentrations of LH and FSH in seven hypocretin-deficient narcoleptic males ( N ) and seven controls ( C ) matched for age , body mass index , and sex . Basal plasma concentrations of testosterone , estradiol , and sex hormone-binding globulin were similar in both groups . Mean 24-h LH concentration was significantly lower in narcolepsy patients [ 3.0 + /- 0.4 ( N ) vs. 4.2 + /- 0.3 ( C ) U/l , P = 0.01 ] , which was primarily due to a reduction of pulsatile LH secretion [ 23.5 + /- 1.6 ( N ) vs. 34.3 + /- 4.9 ( C ) U.l(-1).24 h(-1 ) , P = 0.02 ] . The orderliness of LH and FSH secretion , quantitated by the approximate entropy statistic , was greater in patients than in controls . In contrast , all other features of FSH release were similar in narcoleptic and control groups . Also , LH and FSH secretions in response to intravenous administration of 100 microg of GnRH were similar in patients and controls . These data indicate that endogenous hypocretins are involved in the regulation of the hypothalamo-pituitary-gonadal axis activity in humans . In particular , reduced LH release in the face of normal pituitary responsivity to GnRH stimulation in narcoleptic men suggests that hypocretins promote endogenous GnRH secretion Abstract Aim : In the current study , we aim ed to investigate whether serum orexin-A ( OXA ) levels are different in polycystic ovary syndrome ( PCOS ) subjects . Material s and methods : Thirty-six women with PCOS and 40 healthy , age and body mass index-matched controls were included in the prospect i ve cross-sectional study . All subjects underwent venous blood draws during the early follicular phase after overnight fasting . Serum OXA levels were measured with an enzyme immunoassay ( EIA ) . The relationships between the serum OXA levels and the anthropometric and metabolic parameters were also assessed . Results : The serum OXA levels were lower in the women with PCOS compared to the control group . The serum OXA levels were correlated negatively with systolic blood pressure , the Ferriman-Gallway score and LH and free testosterone levels . Conclusion : Our results indicate that serum OXA levels decrease in the serum of women with PCOS STUDY OBJECTIVES Obesity is a common feature of narcolepsy . In addition , an increased occurrence of non-insulin dependent diabetes has been reported . So far , it is not known whether glucose metabolism in narcolepsy is disturbed due to , or independently of obesity . DESIGN Case-control study . SETTING Sleep medicine clinic at a research institute . PATIENTS We studied 17 patients with narcolepsy/cataplexy compared to 17 healthy controls matched for age , sex , and body mass index ( BMI ) . INTERVENTIONS A 75-g oral glucose tolerance test was performed . MEASUREMENTS Glucose tolerance was determined by computing plasma glucose curve following oral glucose challenge for 240 minutes ; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis . RESULTS St and ard outcome measures and indices of the oral glucose tolerance test did not differ between the patient group and the group of control subjects . CONCLUSIONS In this study , no clinical ly relevant pathologic findings in the glucose metabolism of narcoleptic patients compared to weight matched controls were found . Thus , narcolepsy is unlikely to be a risk factor per se for impaired glucose tolerance or diabetes OBJECTIVE Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy ( MHT ) . The mechanisms mediating these effects remain unclear . Orexin A ( OxA ) is a neuro-peptide that regulates sleep/wakefulness , food intake and metabolism . This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study ( KEEPS ) . METHODS KEEPS r and omized women within three years of menopause to : oral conjugated equine estrogen ( o-CEE , 0.45mg/day ) , transdermal 17β estradiol ( t-E2 , 50μg/day ) , or placebo pills and patches for four years . Plasma OxA levels were measured by enzyme immunoassays in fasting blood sample s collected annually from KEEPS participants at Mayo Clinic during and three years after MHT . Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences . RESULTS During treatment , OxA levels increased more in women r and omized to o-CEE compared with the other groups . Women r and omized to either form of MHT demonstrated smaller increases in BMI than those on placebo . Insomnia severity decreased similarly among treatment groups . However , neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels . Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments . CONCLUSIONS Although OxA levels increased only in women r and omized to o-CEE , these changes did not correlate with changes in sleep quality or BMI . The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol . Clinical Trial Registration for KEEPS : NCT00154180 AIMS To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus , and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months . METHODS This study was design ed as a r and omized , open-label , clinical trial . Before allocation , sixty medication-naïve , newly-diagnosed , type 2 diabetes patients underwent a 75 g oral glucose tolerance test ( OGTT ) . Afterwards , using a r and omized trial design ( I RCT 201102275917N1 ) patients were allocated to either the metformin ( 1000 mg daily ) or pioglitazone ( 30 mg daily ) arm , and were reexamined after three months . Serum insulin , plasma glucose , and orexin concentrations were measured at baseline , during OGTT , and after three months . RESULTS Orexin concentrations significantly decreased after OGTT ( 0 vs. 120 min : 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml , p < 0.001 ) . Insulin resistance determined by homeostasis model assessment of insulin resistance ( HOMA-IR ) was significantly and negatively correlated with orexin ( r = -0.301 , p = 0.024 ) . Furthermore , orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT ( r = 0.326 , p = 0.014 ) . Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26 % ( p = 0.025 ) and 14 % ( p = 0.076 ) , respectively . Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different ( p = 0.742 ) . CONCLUSIONS There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients . Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control BACKGROUND Sleep-disordered breathing ( SDB ) is linked to adverse pregnancy outcomes . However , little is known about the association of SDB with timing of delivery . We examined the association of snoring frequency , a key SDB marker , and snoring intensity , a correlate of SDB severity , with time-to-delivery among a cohort of pregnant women . METHODS In this prospect i ve cohort study , 1483 third trimester pregnant women were recruited from the University of Michigan prenatal clinics . Women completed a question naire about their sleep , and demographic and pregnancy information was abstract ed from medical charts . After exclusion of those with hypertension or diabetes , 954 women were classified into two groups by their snoring onset timing , chronic or pregnancy-onset . Within each of these groups , women were divided into four groups based on their snoring frequency and intensity : non-snorers ; infrequent-quiet ; frequent-quiet ; or frequent-loud snorers . Cox proportional hazard regression models were used to investigate the association between snoring frequency and intensity and time-to-delivery , adjusting for maternal characteristics . RESULTS Chronic snoring was reported by half of the pregnant women , and of those , 7 % were frequent-loud snorers . Deliveries before 38 weeks ' gestation are completed occurred among 25 % of women with chronic , frequent-loud snoring . Compared with pre-pregnancy non-snorers , women with chronic frequent-loud snoring had an increased hazard ratio for delivery ( adjusted hazard ratio 1.60 , 95 % confidence interval 1.04 , 2.45 ) . CONCLUSIONS Snoring frequency and intensity is associated with time-to-delivery in women absent of hypertension or diabetes . Frequent-loud snoring may have a clinical utility to identify otherwise low-risk women who are likely to deliver earlier |
454 | 28,302,699 | Conclusions Specific psychological and psychosocial interventions have utility in ameliorating negative symptoms in psychosis and should be included in the treatment of negative symptoms . | Background Negative symptoms observed in patients with psychotic disorders undermine quality of life and functioning .
Antipsychotic medications have a limited impact .
Psychological and psychosocial interventions , with medication , are recommended .
However , evidence for the effectiveness of specific non-biological interventions warrants detailed examination .
Aims To conduct a meta-analytic and systematic review of the literature on the effectiveness of non-biological treatments for negative symptoms in psychotic disorders . | BACKGROUND Antipsychotic drugs are usually the first line of treatment for schizophrenia ; however , many patients refuse or discontinue their pharmacological treatment . We aim ed to establish whether cognitive therapy was effective in reducing psychiatric symptoms in people with schizophrenia spectrum disorders who had chosen not to take antipsychotic drugs . METHODS We did a single-blind r and omised controlled trial at two UK centres between Feb 15 , 2010 , and May 30 , 2013 . Participants aged 16 - 65 years with schizophrenia spectrum disorders , who had chosen not to take antipsychotic drugs for psychosis , were r and omly assigned ( 1:1 ) , by a computerised system with permuted block sizes of four or six , to receive cognitive therapy plus treatment as usual , or treatment as usual alone . R and omisation was stratified by study site . Outcome assessors were masked to group allocation . Our primary outcome was total score on the positive and negative syndrome scale ( PANSS ) , which we assessed at baseline , and at months 3 , 6 , 9 , 12 , 15 , and 18 . Analysis was by intention to treat , with an ANCOVA model adjusted for site , age , sex , and baseline symptoms . This study is registered as an International St and ard R and omised Controlled Trial , number 29607432 . FINDINGS 74 individuals were r and omly assigned to receive either cognitive therapy plus treatment as usual ( n=37 ) , or treatment as usual alone ( n=37 ) . Mean PANSS total scores were consistently lower in the cognitive therapy group than in the treatment as usual group , with an estimated between-group effect size of -6.52 ( 95 % CI -10.79 to -2.25 ; p=0.003 ) . We recorded eight serious adverse events : two in patients in the cognitive therapy group ( one attempted overdose and one patient presenting risk to others , both after therapy ) , and six in those in the treatment as usual group ( two deaths , both of which were deemed unrelated to trial participation or mental health ; three compulsory admissions to hospital for treatment under the mental health act ; and one attempted overdose ) . INTERPRETATION Cognitive therapy significantly reduced psychiatric symptoms and seems to be a safe and acceptable alternative for people with schizophrenia spectrum disorders who have chosen not to take antipsychotic drugs . Evidence -based treatments should be available to these individuals . A larger , definitive trial is needed . FUNDING National Institute for Health Research BACKGROUND The effectiveness of a psychosocial skills training ( PSST ) approach applied to chronic out- patients with schizophrenia was examined . We hypothesized that the PSST programme , which included treatment as usual ( TAU ) , PSST and family therapy ( FT ) , would reduce positive and negative symptoms , prevent relapse and rehospitalization , and improve psychosocial functioning ( PSF ) , global functioning and treatment adherence . METHOD Eighty-two patients were r and omly assigned to receive either TAU [ antipsychotic medication ( AP ) ; n=39 ] or the PSST approach ( TAU+PSST+FT ; n=43 ) . The two groups were assessed at intake and after completion of 1 year of treatment . RESULTS There were statistically significant differences between the two groups . Patients in the PSST group improved their symptomatology , psychosocial and global functioning ( symptoms and psychological , social and occupational functioning ) , showed lower relapse , rehospitalization and drop-out rates , a higher level of compliance with AP medication , and a high level of therapeutic adherence in comparison with TAU patients , whose symptoms also improved although they showed no improvement in any of the clinical or psychosocial variables . A comparison of the st and ardized effect sizes showed a medium and a large effect size of PSF and global functioning for the PSST group and a non-effect size for the TAU group . CONCLUSIONS A higher level of effectiveness was demonstrated when combining TAU , PSST and FT in comparison with AP medication alone . The PSST approach should be recommended for clinical practice OBJECTIVE The present study aims to assess the efficacy of a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families . The intervention was implemented in parallel in 2 separate groups by focusing specifically on problem-solving strategies and structured psychosis-related information to manage daily life difficulties associated with the disease , to mitigate crises , and to prevent relapses . METHOD We performed a 9-month , r and omized , rater-blinded clinical trial involving 55 adolescent patients with early-onset psychosis and either or both of their parents . A psychoeducational problem-solving group intervention ( n = 27 ) was compared with a nonstructured group intervention ( n = 28 ) . The primary outcomes were number of hospitalizations , days of hospitalization , and visits to the emergency department . The secondary outcome measures were clinical variables and family environment . RESULTS Assessment s were performed before and after the intervention . At the end of the group intervention , 15 % of patients in the psychoeducational group and 39 % patients in the nonstructured group had visited the emergency department ( χ² = 3.62 , df = 1 , p = .039 ) . The improvement in negative symptoms was more pronounced in the psychoeducational group ( 12.84 [ 7.87 ] ) than in the nonstructured group ( 15.81 [ 6.37 ] ) ( p = .039 ) . CONCLUSION A parallel psychoeducational group intervention providing written instructions in a structured manner could help adolescents with early-onset psychosis and their parents to manage crises by implementing problem-solving strategies within the family , thus reducing the number of visits to the emergency department . Negative symptoms improved in adolescents in the psychoeducational group . Clinical trial registration information -- Intervention Module AGES ( AGES-CM ) ; http:// clinical trials.gov/ ; NCT02101372 . [ corrected ] Objectives : To investigate the effectiveness of a long established intervention , occupational therapy for people with psychotic conditions , and to inform future research design s. Design : A pilot r and omized controlled trial . Setting : Two community mental health teams in a UK city . Participants : Forty-four adults with schizophrenia or other psychotic conditions , and functional problems . Interventions : Twelve months of individualized occupational therapy in community setting s , as an adjunct to usual care and compared to treatment as usual . A two to one r and omization ratio was used in favour of occupational therapy . Outcome measures : Social Functioning Scale , Scale for the Assessment of Negative Symptoms and employment . Results : Both groups ' scores on Social Functioning Scale and Scale for the Assessment of Negative Symptoms showed significant improvement over 12 months . The Social Functioning Scale overall mean difference for occupational therapy was 2.33 , P=0.020 and for treatment as usual was 6.17 , P=0.023 . The Scale for the Assessment of Negative Symptoms total mean difference for occupational therapy was -16.25 , P<0.001 and for treatment as usual was -17.36 , P= 0.011 . There were no differences between the two groups on any of the outcome measures . After 12 months the occupational therapy group showed clinical ly significant improvements that were not apparent in the control group . These were in four subscales of the Social Functioning Scale : relationships , independence performance , independence competence and recreation . Out of 30 people receiving occupational therapy those with a clinical level of negative symptoms reduced from 18 ( 64 % ) to 13 ( 46 % ) , P=0.055 . Conclusion : This pilot study suggested that individualized occupational therapy may contribute to recovery but more focus is recommended on people 's cognitive abilities and employment This r and omised clinical trial assessed the effects of a 16‐week cognitive remediation programme ( NEUROCOM ) combined with an early intervention service ( EIS ) vs. EIS alone BACKGROUND There is increasing evidence that cognitive-behavioural therapy can be an effective intervention for patients experiencing drug-refractory positive symptoms of schizophrenia . AIMS To investigate the effects of cognitive-behavioural therapy on in- patients with treatment-refractory psychotic symptoms . METHOD Manualised therapy was compared with supportive counselling in a r and omised controlled study . Both interventions were delivered by experienced psychologists over 16 sessions of treatment . Therapy fidelity was assessed by two independent raters . Participants underwent masked assessment at baseline , after treatment and at 6 months ' follow-up . Main outcome measures were the Positive and Negative Syndrome Scale and the Psychotic Symptoms Rating Scale . The analysis was by intention to treat . RESULTS Participants receiving cognitive cognitive-behavioural therapy had improved with regard to auditory hallucinations and illness insight at the post-treatment assessment , but these findings were not maintained at follow-up . CONCLUSIONS Cognitive-behavioural therapy showed modest short-term benefits over supportive counselling for treatment-refractory positive symptoms of schizophrenia OBJECTIVE Cognitive remediation ( CR ) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia . However , there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome . METHOD This 8-site r and omized controlled trial evaluated the efficacy of a novel CR group therapy approach called integrated neurocognitive therapy ( INT ) . INT includes well-defined exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia ( MATRICS ) initiative by compensation and restitution . One hundred and fifty-six out patients with a diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV-TR or ICD-10 were r and omly assigned to receive 15 weeks of INT or treatment as usual ( TAU ) . INT patients received 30 bi-weekly therapy sessions . Each session lasted 90min . Mixed models were applied to assess changes in neurocognition , social cognition , symptoms , and functional outcome at post-treatment and at 9-month follow-up . RESULTS In comparison to TAU , INT patients showed significant improvements in several neuro- and social-cognitive domains , negative symptoms , and functional outcome after therapy and at 9-month follow-up . Number-needed-to-treat analyses indicate that only 5 INT patients are necessary to produce durable and meaningful improvements in functional outcome . CONCLUSIONS Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome . These findings are important as treatment guidelines for schizophrenia have criticized CR for its poor generalization effects BACKGROUND There is good evidence now that cognitive behaviour therapy ( CBT ) is effective in the treatment of people suffering from schizophrenia . There is also some evidence that the benefits of CBT persist after the end of treatment and that the direct costs of providing CBT as an adjunct to st and ard care are no higher than the direct costs of st and ard care alone . The aims of the present study were to discover if the benefits of CBT for acute schizophrenia which were found 1 year after index admission persist for another year , and to evaluate the comparative costs of providing CBT . METHOD Consecutive admissions meeting criteria were recruited . After screening , 43 were assigned at r and om to a treatment-as-usual ( TAU ) control group and 47 were assigned to TAU plus CBT . Patients ( 73 % of original ) were rated on symptoms and social functioning 2 years after index admission . An evaluation of the direct costs of services was also completed . RESULTS The CBT group had maintained its advantage over the TAU group on negative symptoms and social functioning but had lost the advantage it previously enjoyed in positive symptoms . The difference between groups in total direct costs over the 2 years was not statistically significant despite the cost of providing CBT . CONCLUSIONS Some of the benefits of CBT for patients suffering acute psychotic episodes persist for 2 years . After the end of regular treatment , CBT should probably be targeted on the appearance of early signs of relapse to forestall the re-emergence of positive symptoms Background : Lifestyle moderate-intensity physical activity can lower the risk of over twenty chronic health conditions , whilst inactivity reduces daily functioning and physical health of individuals living with schizophrenia . This study conducted in 2014 examines the effect of structured walking participation on QOL , psychosocial functioning and symptoms in Hospital Permai , one of the largest psychiatry institution in Asia Method : Chronic patients with schizophrenia ( n=104 ) who met inclusion criteria were r and omised to either a 3-month structured walking intervention or a treatment-as-usual arm . The Positive and Negative Syndrome Scale ( PANSS ) , global functioning ( PSP ) and QOL ( SF-36 ) were measured at baseline and after the 3-month interval . Results : At 3 month follow-up , there were significant within group differences in QOL ( SF-36 ) , psychiatric symptoms ( PANSS ) , and personal and social performance ( PSP ) . There were statistically significant increase in the median SF-36 scores , with increases shown in physical functioning ( p<.001 ) , physical role limitations ( p<.05 ) , social functioning ( p<.01 ) in the intervention group compared to treatment-as-usual group . Statistically significant reduction of median PANSS score of the intervention group were noted in positive ( p<0.001 ) and negative ( p<0.01 ) symptom , and general psychopathology ( p<0.01 ) scales . Statistically significant increase in the median PSP score ( p<0.01 ) was found in the intervention group compared with the treatment-as-usual group . Between-group differences at post intervention ( favouring Intervention ) were significant for PANSS positive and SF36 Physical Conclusion : In long stayed chronic inmates , a simple but consistent , organized walking intervention has the potential to bring improvement in functioning , reduction in psychiatric symptoms and quality of Life . The emphasis of rehabilitation should target at lifestyle re design intervention Objective . Patients with schizophrenia residing at institutions often suffer from negative symptoms , motor , and functional impairments more severe than their noninstitutionalized counterparts . Tai-chi emphasizes body relaxation , alertness , and movement coordination with benefits to balance , focus , and stress relief . This pilot study explored the efficacy of Tai-chi on movement coordination , negative symptoms , and functioning disabilities towards schizophrenia . Methods . A r and omized waitlist control design was adopted , where participants were r and omized to receive either the 6-week Tai-chi program and st and ard residential care or only the latter . 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency . All were assessed on movement coordination , negative symptoms , and functional disabilities at baseline , following intervention and 6 weeks after intervention . Results . Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning , the latter with sustained effectiveness 6 weeks after the class was ended . Controls showed marked deteriorations in those areas . The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance . There was no significant improvement in negative symptoms after Tai-chi . Conclusions . This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia . The ease of implementation facilitates promotion at institutional psychiatric services Background Antipsychotic medication has limited abilities to improve the cognitive impairments that accompany schizophrenia . Adding psychosocial treatment may result in marked improvements in cognitive function , as compared to antipsychotic treatment alone . We hypothesized that a combination of individual and family interventions may be a useful cognitive rehabilitation paradigm for schizophrenia . Material s and methods An 18-month follow-up clinical trial of 256 stabilized patients with schizophrenia at six communities in Shanghai , People ’s Republic of China were r and omly assigned to into either a comprehensive family therapy ( CFT ) group or a usual daily care ( UDC ) group . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) and the Positive and Negative Syndrome Scale ( PANSS ) were the primary outcome instruments for this study . Results There was no significant difference between the CFT and UDC for all demographic characteristics at the baseline assessment . During the 18-month follow-up observation , changes in RBANS total score indicated that patients undergoing CFT showed greater improvement from baseline to the follow-up assessment s in cognitive function than those in the UDC group ( F=9.77 , P=0.002 ) . Post hoc analysis showed that the CFT group presented with significant differences in the RBANS total score , immediate memory , visuospatial skill , language , attention , and delayed memory sections compared with the UDC after 18 months of follow-up ( all P<0.01 ) . Conclusion Our findings suggest that CFT can be easily adapted and may prove to be an effective approach for improving cognitive function in patients with schizophrenia . Our program provides a potential paradigm for cognitive rehabilitation for schizophrenia patients in the community OBJECTIVE To examine the effects of Hatha yoga therapy on resilience , brain-derived neurotrophic factor ( BDNF ) levels , and salivary alpha amylase ( SAA ) activity in patients with schizophrenia-spectrum disorders . DESIGN AND PARTICIPANTS Single-blinded , r and omized controlled study in which out patients with schizophrenia or related psychotic disorders ( according to International Classification of Diseases , 10th Revision ) were r and omly assigned to a yoga or a control group . SETTING November 2012-April 2013 at Yamanashi Prefectural Kita Hospital , Japan . INTERVENTIONS In the yoga group , patients received weekly 1-hour Hatha yoga sessions , in addition to regular treatment , for 8 weeks . Those in the control group underwent regular treatment , which included a daycare rehabilitation program . OUTCOME MEASURES Assessment s included the 25-item Resilience Scale ( RS ) , Positive and Negative Syndrome Scale ( PANSS ) , plasma and salivary BDNF level , and SAA activity . RESULTS Fifty patients participated ( 25 in each group ; mean age±st and ard deviation , 50.9±11.3 years ; mean duration of illness , 25.0±10.3 years ; mean total PANSS score , 78.2±17.3 ) . No significant differences in changes in any variable from baseline to week 8 were found between the two groups ( changes in the yoga group versus the control group : RS score , -1.6±19.9 versus 0.3±17.2 ; PANSS score , 0.5±12.0 versus 5.0±15.6 ; plasma BDNF , 41.6±377.0 pg/dl versus 73.4±346.0 pg/dl ; SAA , -26.2±72.6 kU/l versus -13.8±68.0 kU/l , respectively ) . CONCLUSIONS Adjunct yoga therapy showed no positive changes in resilience level or stress markers . Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy Psychoeducational medication management training ( PMT ) , cognitive psychotherapy ( CP ) and key‐person counselling ( KC ) were carried out in various combinations in this r and omized , controlled intervention study of schizophrenic out‐ patients ( according to DSM‐III‐R ) . Special design characteristics of the study were a control group consisting of non‐specifically treated patients and a 2‐year follow‐up after completion of treatment in order to evaluate medium‐term effects . A total of 132 patients underwent a follow‐up examination 2 years after completion of treatment and were evaluated with an intention‐to‐treat approach . In the second follow‐up year , all treatment groups had lower but not significantly different relapse rates compared to the control group . The most intensive treatment ( PMT+CP+KC ) produces a clinical ly relevant reduction in rehospitalization rate ( a 26 % reduction compared to the control group ) . In comparison with the non‐specifically treated control group , whose original effect decreased , at least a medium‐term therapeutic effect was recorded in the treatment groups BACKGROUND The initial phase of a trial of cognitive-behavioural therapy ( CBT ) for acutely ill patients with schizophrenia of recent onset showed that it speeded recovery . AIMS To test the hypothesis that CBT in addition to treatment as usual ( TAU ) during the first or second acute episode of schizophrenia will confer clinical benefit over a follow-up period . METHOD This was an 18-month follow-up of a multicentre prospect i ve trial of CBT or supportive counselling administered as an adjunct to TAU , compared with TAU alone , for patients hospitalised for an acute episode of schizophrenia of recent onset . Primary outcomes were total and positive symptom scales , time to relapse and re-hospitalisation . RESULTS There were significant advantages for CBT and supportive counselling over TAU alone on symptom measures at 18 months but no group difference was seen for relapse or re-hospitalisation . There was a significant centre-treatment interaction , reflecting centre differences in the effect of introducing either treatment , but not in the comparison of CBT and supportive counselling . Medication dosage and compliance did not explain group differences . CONCLUSIONS Adjunctive psychological treatments can have a beneficial long-term effect on symptom reduction Low self esteem in individuals with a psychotic disorder is common and may be related to poorer clinical outcomes . However , there has been little research on devising treatment methods to improve self-esteem either generally or in psychotic patients in particular . The aims of this study were to evaluate the efficacy of a simple cognitive behavioural intervention to improve self esteem in psychotic patients who scored poorly on a self-esteem measure . This pilot study was a r and omised control trial with a convenience sample of chronic psychotic in patients . The cognitive behavioural self-esteem intervention , as an adjunct to treatment as usual ( TAU ) , was compared to TAU alone in patients with psychosis . The individual self-esteem intervention as described by Tarrier ( The use of coping strategies and self-regulation in the treatment of psychosis . ( 2001 ) ) consisted of working with participants to elicit positive self-attributes and then identify specific behavioural examples to provide evidence of this attribute . Emphasis was given to any consequential change in the patient 's belief that they had the attribute . The results indicated that this cognitive behavioural treatment for self-esteem used as an adjunct treatment in psychosis , result ed in clinical benefits in terms of increased self-esteem , decreased psychotic symptomatology and improved social functioning . These benefits were largely maintained at 3-month follow-up BACKGROUND The aim of the current study was to assess whether patients with a DSM-IV diagnosis of schizophrenia and experiencing persistent positive and negative symptoms improve with the addition of cognitive-behavioural therapy to enriched st and ard treatment . METHODS A controlled study was completed with 42 patients r and omized to either cognitive-behavioural therapy plus enriched treatment-as-usual ( CBT-ETAU ) ( n = 24 ) or enriched treatment-as-usual only ( ETAU ) ( n = 18 ) . Enriched treatment-as-usual comprised comprehensive treatment within specialised schizophrenia treatment services . Cognitive-behavioural therapy was conducted on an individual basis for 6 months ( 20 sessions ) . Clinical assessment s were done at pretreatment , posttreatment and at 6-month follow-up by raters blind to group allocation . RESULTS Significant clinical effects were observed for positive , negative and overall symptom severity for patients treated in CBT-ETAU , although there were no statistically significant differences between the treatment groups at posttreatment . The most pronounced effect of CBT-ETAU in comparison to ETAU in this study was in the reduction of negative symptoms at follow-up . CONCLUSION These results show promise for the impact of CBT on negative symptoms when explicitly targeted in treatment BACKGROUND The feasibility and preliminary efficacy of a novel cognitive behavioral treatment for decreasing psychotic symptoms and improving social functioning was evaluated in a pilot study . This represents the first treatment outcome study of CBT for psychosis with a manualized , active comparison condition . METHODS Thirty out patients with schizophrenia or schizoaffective disorder , depressed type with residual psychotic symptoms were r and omly assigned to either 16 weekly sessions of functional cognitive behavioral therapy ( fCBT ) or psychoeducation ( PE ) with assessment s conducted at baseline and post-treatment by blind evaluators . RESULTS Attrition was only 7 % and did not differ between fCBT and PE , indicating good tolerability of both treatments . For this sample with persistent symptoms , between groups effects were not significantly different , but within group effect sizes indicated greater treatment benefit for fCBT on positive symptoms , particularly for the PSYRATS voices subscale . CONCLUSION The results suggest that fCBT is well tolerated and holds promise for reducing persistent positive symptoms Evidence for the effectiveness of Culturally adapted CBT for psychosis in Low And Middle Income Countries ( LAMIC ) is limited . Therefore , brief Culturally adapted CBT for psychosis ( CaCBTp ) targeted at symptoms of schizophrenia for out patients plus treatment as usual ( TAU ) is compared with TAU . A total of 116 participants with schizophrenia were recruited from 2 hospitals in Karachi , Pakistan , and r and omized into two groups with 1:1 allocation ( CaCBTp plus TAU=59 , TAU=57 ) . A brief version of CaCBTp ( 6 individual sessions with the involvement of main carer , plus one session for the family ) was provided over 4months . Psychopathology was measured using Positive and Negative Syndrome Scale of Schizophrenia ( PANSS ) , Psychotic Symptom Rating Scales ( PSYRATS ) , and the Schedule for Assessment of Insight ( SAI ) at baseline and end of therapy . Participants in treatment group , showed statistically significant improvement in all measures of psychopathology at the end of the study compared with control group . Participants in treatment group showed statistically significant improvement in Positive Symptoms ( PANSS , Positive Symptoms Subscale ; p=0.000 ) , Negative Symptoms ( PANSS , Negative Symptoms subscales ; p=0.000 ) , Delusions ( PSYRATS , Delusions Subscale ; p=0.000 ) , Hallucinations ( PSYRATS , Hallucination Subscale ; p=0.000 ) and Insight ( SAI ; p=0.007 ) . The results suggest that brief , Culturally adapted CBT for psychosis can be an effective treatment when provided in combination with TAU , for patients with schizophrenia in a LAMIC setting . This is the first trial of CBT for psychosis from outside the western world . These findings need replicating in other low and middle income countries Background : Cognitive behavioural therapy for psychosis ( CBTp ) is currently a recommended form of psychosocial treatment for persons suffering from persistent psychotic symptoms . It has been argued that effect sizes from efficacy studies can not be generalized to real clinical setting s. Aims : Our aim was to evaluate whether the positive results from r and omized controlled trials conducted by experts could be replicated in clinical setting with a heterogeneous sample of patients with psychotic disorder . Method : Patients referred to the study were either r and omized to CBTp + TAU ( the treatment group ) or to a waiting-list group , only receiving TAU . The patients were assessed on different outcome measures such as the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment of Negative Symptoms ( SANS ) , and the Psychotic Symptom Rating Scales ( PSYRATS ) , at pretreatment , at posttreatment ( 6 months ) , and at 12 months follow-up . In total , 45 patients participated in the study . Results : The results showed that 20 sessions of CBTp performed significantly better than the waiting list controls with respect to the global score on the BPRS , the delusional scale on the PSYRATS , and the GAF symptom score at posttreatment . At 12 months follow-up only the GAF symptom score remained significantly changed for the total sample . Conclusions : The study revealed that CBTp delivered by non-experts in routine clinical setting s can produce improvements in positive psychotic symptoms , and also that some of these improvements can be maintained at one year follow-up OBJECTIVE To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms , quality of life outcomes , and serum IGF-1 , IGFBP-3 , and brain-derived neurotrophic factor ( BDNF ) concentrations in patients with schizophrenia . METHODS In this blind , r and omized controlled clinical trial , 34 patients with schizophrenia were assigned to one of three groups : control ( CTRL , n=13 ) , resistance exercise ( RESEX , n=12 ) , or concurrent exercise ( CONCEX , n=9 ) . Symptoms , quality of life , strength , and other variables were assessed . RESULTS A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale ( PANSS ) total score for disease symptoms ( p = 0.007 ) , positive symptoms ( p = 0.003 ) , and on the arm extension one-repetition maximum ( 1RM ) test ( p = 0.016 ) . In addition , significant improvements on negative symptoms ( p = 0.027 ) , on the role-physical domain of the Short Form-36 Health Survey ( p = 0.019 ) , and on the chest press 1RM test ( p = 0.040 ) were observed in the RESEX group . No changes were observed for the other variables investigated . CONCLUSIONS In this sample of patients with schizophrenia , 20 weeks of resistance or concurrent exercise program improved disease symptoms , strength , and quality of life . Clinical Trials.gov : NCT01674543 BACKGROUND Little is known about the medium-term durability of cognitive-behavioural therapy ( CBT ) in a community sample of people with schizophrenia . AIMS To investigate whether brief CBT produces clinical ly important outcomes in relation to recovery , symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up . METHOD Participants ( 336 of 422 r and omised at baseline ) were followed up at a mean of 388 days ( s.d . = 53 ) by raters masked to treatment allocation ( CBT or usual care ) . RESULTS At 1-year follow-up , participants who received CBT had significantly more insight ( P = 0.021 ) and significantly fewer negative symptoms ( P = 0.002 ) . Brief therapy protected against depression with improving insight and against relapse ; significantly reduced time spent in hospital for those who did relapse and delayed time to admission . It did not improve psychotic symptoms or occupational recovery , nor have a lasting effect on overall symptoms or depression at follow-up . CONCLUSIONS Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management , family interventions and expert therapy for treatment resistance BACKGROUND The paper describes a r and omized controlled trial of targeting cognitive behavioural therapy ( CBT ) during prodromal or early signs of relapse in schizophrenia . We hypothesized that CBT would result in reduced admission and relapse , reduced positive and negative symptoms , and improved social functioning . METHOD A total of 144 participants with schizophrenia or a related disorder were r and omized to receive either treatment as usual ( TAU ) ( N = 72 ) or CBT+TAU ( N = 72 ) . Participants were prospect ively followed up between entry and 12 months . RESULTS At 12 months , 11 ( 15.3 % ) participants in the CBT group were admitted to hospital compared to 19 ( 26.4 % ) of the TAU group ( hazard ratio = 0.53 , P = 0.10 , 95 % CI 0.25 , 1.10 ) . A total of 13 ( 18.1 % ) participants in CBT relapsed compared to 25 ( 34.7 % ) in TAU ( hazard ratio = 0.47 , P < 0O05 , 95 % CI 0.24 , 0.92 ) . In addition , the CBT group showed significantly greater improvement in positive symptoms , negative symptoms , global psychopathology , performance of independent functions and prosocial activities . CONCLUSIONS The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia . The results are discussed in context of the study 's method ological limitations Cognitive dysfunctions and negative symptoms are " rate-limiting factors " for community outcome and response to psychosocial intervention in people with schizophrenia . Therefore , two cognitive-behavioral group therapies were developed-computer-assisted cognitive strategy training ( CAST ) and training of self-management skills for negative symptoms (TSSN)-to target these barriers to rehabilitation readiness . One hundred thirty-eight DSM-IV schizophrenia in patients on a rehabilitation ward were r and omly assigned to CAST plus vocational rehabilitation , TSSN plus vocational rehabilitation , or vocational rehabilitation alone . CAST included computer-based training in coping strategies focusing on deficits in attention , verbal memory , and planning . TSSN focused on social withdrawal/social anhedonia , lack of drive/volition , and affect flattening using techniques such as time scheduling , mastery , and pleasure techniques . Treatment outcome was assessed at intake and at discharge after 8 weeks . Analyses of covariance controlling for basis-level functioning demonstrated that patients receiving CAST plus vocational rehabilitation showed greater improvement on attention and verbal memory but not on planning ability . Patients receiving TSSN plus vocational rehabilitation failed to demonstrate improvement in negative symptoms . CAST plus vocational rehabilitation was found to be associated with a higher rate of successful job placement at the 12-month followup interval . Hierarchical logistic regression analyses demonstrated that improvement in short- and long-term verbal memory predicted a higher proportion of variance of successful job placement in the followup than pretreatment history of employment alone . Cognitive training as an adjunct to inpatient vocational rehabilitation demonstrated cognitive improvement , which was found to be associated with successful job placement in the followup . TSSN 's efficacy was less clear ; reasons for this uncertainty are provided This pilot study aim ed to evaluate the feasibility of an assessor-blind , r and omised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia , and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes . Fifty-eight in patients with DSM-diagnoses of schizophrenia were r and omised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to st and ard treatment alone . Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning . Secondary outcomes were mentalising function , estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale , self-efficacy , locus of control , quality of life and satisfaction with care . Assessment s were made at baseline , at post-treatment and at 12 weeks ' follow-up . At 12 weeks , 55 % of patients r and omised to art therapy , and 66 % of patients receiving treatment as usual were examined . In the per- protocol sample , art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up , and with a greater mean reduction of negative symptoms at follow-up compared to st and ard treatment . The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis . There were no group differences regarding depressive symptoms . Of secondary outcome parameters , patients in the art therapy group showed a significant improvement in levels of emotional awareness , and particularly in their ability to reflect about others ' emotional mental states . This is one of the first r and omised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment . Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function . Trial Registration Clinical Trials.gov CONTEXT Low-functioning patients with chronic schizophrenia have high direct treatment costs and indirect costs incurred due to lost employment and productivity and have a low quality of life ; antipsychotic medications and psychosocial interventions have shown limited efficacy to promote improved functional outcomes . OBJECTIVE To determine the efficacy of an 18-month recovery-oriented cognitive therapy program to improve psychosocial functioning and negative symptoms ( avolition-apathy , anhedonia-asociality ) in low-functioning patients with schizophrenia . Design , Setting , and PARTICIPANTS A single-center , 18-month , r and omized , single-blind , parallel group trial enrolled 60 low-functioning , neurocognitively impaired patients with schizophrenia ( mean age , 38.4 years ; 33.3 % female ; 65.0 % African American ) . INTERVENTIONS Cognitive therapy plus st and ard treatment vs st and ard treatment alone . MAIN OUTCOME MEASURES The primary outcome measure was the Global Assessment Scale score at 18 months after r and omization . The secondary outcomes were scores on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms at 18 months after r and omization . RESULTS Patients treated with cognitive therapy showed a clinical ly significant mean improvement in global functioning from baseline to 18 months that was greater than the improvement seen with st and ard treatment ( within-group Cohen d , 1.36 vs 0.06 , respectively ; adjusted mean [ SE ] , 58.3 [ 3.30 ] vs 47.9 [ 3.60 ] , respectively ; P = .03 ; between-group d = 0.56 ) . Patients receiving cognitive therapy as compared with those receiving st and ard treatment also showed a greater mean reduction in avolition-apathy ( adjusted mean [ SE ] , 1.66 [ 0.31 ] vs 2.81 [ 0.34 ] , respectively ; P = .01 ; between-group d = -0.66 ) and positive symptoms ( hallucinations , delusions , disorganization ) ( adjusted mean [ SE ] , 9.4 [ 3.3 ] vs 18.2 [ 3.8 ] , respectively ; P = .04 ; between-group d = -0.46 ) at 18 months . Age was controlled in the analyses , and there were no meaningful group differences in baseline antipsychotic medications ( class or dosage ) or in medication changes during the course of the trial . CONCLUSION Cognitive therapy can be successful in promoting clinical ly meaningful improvements in functional outcome , motivation , and positive symptoms in low-functioning patients with significant cognitive impairment . Trial Registration clinical trials.gov Identifier : NCT00350883 Objective : This study was design ed to evaluate the efficacy of psychosocial rehabilitation intervention on schizophrenia . Methodology : One hundred forty schizophrenia out patients in remission stage were r and omized to either an antipsychotic monomedication ( control group ) or an antipsychotic monomedication plus a psychosocial rehabitation training ( trial group ) . Positive and Negative syndrome Scale ( PANSS ) , Disability Screening Schedule ( SDSS ) were performed longitudinally from baseline to month 18 to evaluate the efficacy . Results : Significant difference in relapse rate between the control group ( 42.9 % ) and the trial group ( 18.6 % ) was found at month 18 . In patients who did n’t relapse , the trial group showed significantly lower PANSS and SDSS score ( P<0.05 ) than did the control group after treatment . Conclusion : Psychosocial rehabilitation intervention could produce a better outcome in terms of reducing relapse and improving the social functioning in schizophrenia Individuals with schizophrenia demonstrate deficits in divergent thinking . This ability is indispensable for generating creative solutions and navigating the complexities of social interactions . In a pilot study , seventeen stable schizophrenia out patients were r and omly assigned to a training program for divergent thinking or a control program on convergent thinking . After eight weeks of training , participants in the divergent thinking program had significantly greater improvements on measures of idea fluency , negative symptoms , and interpersonal relations than did participants receiving the control program . These preliminary results suggest that interventions for divergent thinking in schizophrenia may lead to improvements in patients ' social functioning Poor adherence limits the effectiveness of antipsychotic treatment in people with psychosis . The aim of the pragmatic , exploratory , single-masked trial conducted in the USA was to explore the efficacy , acceptability , and satisfaction with adherence therapy ( AT ) in a sample of people with schizophrenia . Twenty-six patients ( 12 experimental and 14 controls ) were r and omly allocated to receive eight weekly sessions of AT or continue with their treatment as usual ( TAU ) . Patients were assessed at baseline and follow up ( after therapy completion ) . The primary outcome was psychiatric symptoms , assessed using the Positive and Negative Syndrome Scale ( PANSS ) . The secondary outcome , medication adherence , was measured by The Personal Evaluation of Transitions in Treatment . Patients receiving AT did not significantly improve in overall psychiatric symptomatology ( change in PANSS total scores : AT : -10.2 , TAU : -8.6 ; mean difference , -1.6 ; P = ns ) or with medication adherence ( AT : -2.8 , TAU 1.5 ; P = ns ) compared with the TAU group at follow up . Using the Adherence Therapy Patient Satisfaction Question naire , a high degree of satisfaction with AT was reported . Although AT did not result in a statistically-significant improvement in symptoms or medication adherence , evidence of active clinical engagement in treatment occurred Several studies in schizophrenia found a positive association between cognitive performance and work status , and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions . However little has been done to investigate whether vocational interventions itself benefit cognitive performance . To test this hypothesis we performed a r and omized , placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance . We recruited 112 remitted and clinical ly stable schizophrenic patients who aim ed to enter a vocational rehabilitation program . From these , 57 immediately entered a 6-months vocational rehabilitation program , whereas the remaining 55 were allocated to a waiting-list ; the latter formed our control group , which received during the 6 months out-clinic follow-up treatment . Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery , as well as changes in the psychopathological status and in quality of life . We found that vocational rehabilitation significantly improved patients ' performance in cognitive measures that assess executive functions ( concept formation , shifting ability , flexibility , inhibitory control , and judgment and critics abilities ) . Moreover , after 6 months the vocational group improved significantly in the negative symptoms and in quality of life , as compared to controls . Together with results from the literature , our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients The objective of this multicenter r and omised clinical trial was to examine the effect of exercise versus occupational therapy on mental and physical health in schizophrenia patients OBJECTIVE This study , which was the first evaluation in Australia of multiple-family group treatment , explored the effectiveness of this approach for a newly arrived non-English speaking migrant group , first-generation Vietnamese families , and for English-speaking families . METHODS Thirty-four pairs of English-speaking consumers and family members and 25 Vietnamese-speaking pairs were r and omly assigned to a multiple-family group or a control group . All consumers had a diagnosis of schizophrenia . The multiple-family group intervention ( 26 sessions over 12 months ) was delivered as an adjunct to case management services , which all consumers received . Outcomes , which were measured immediately after treatment and 18 months later , included the number of relapse episodes ; the presence and severity of symptoms , as measured by the Brief Psychiatric Rating Scale ( BPRS ) and the Scale for the Assessment of Negative Symptoms ; and social functioning , as measured by the Family Burden Scale , the Health of the Nation Outcome Scale , and the Quality of Life Scale . RESULTS Relapse rates immediately after treatment were significantly lower for the multiple-family group than for the control group ( 12 and 36 percent ) , and relapse rates were also lower during the follow-up period ( 25 and 63 percent ) . BPRS ratings were significantly lower for participants in the multiple-family group , and vocational outcomes also improved . The reductions in relapse and symptoms were similar for the English-speaking and the Vietnamese-speaking family groups ; sample size precluded statistical analysis of differences . CONCLUSIONS Multiple-family group treatment is an effective cognitive-behavioral intervention in the treatment of schizophrenia . The findings suggest continued application of and research on family interventions for non-English speaking migrant population Abstract Our team recently conducted a r and omized controlled trial comparing group cognitive behavior therapy for psychosis ( CBTp ) to group social skills training for symptom management and a wait-list control group , for early psychosis . The results at post-therapy and six months provided considerable empirical support for the efficacy of the group CBTp . The results of the one-year follow-up are described here . Given the high attrition rates , mostly in the comparison and control conditions , imputations were not possible , so that only the results of those having completed more than 50 % of the group CBTp are presented . Significant improvements at 12 months were found for social support and insight . Negative symptoms remained low , whereas positive symptoms went back to pre-therapy levels . Challenges regarding attrition with this clientele are discussed BACKGROUND The application of cognitive therapy ( CT ) to psychosis is currently being developed in the UK . This paper reports a trial of CT in acute psychosis with the objective of hastening the resolution of positive symptoms and reducing residual symptoms . METHOD Of 117 patients with acute non-affective psychosis , 69 satisfied inclusion criteria and 40 proceeded to stratified r and omisation . The experimental intervention involving individual and group CT was compared with a group receiving matched hours of therapist input providing structured activities and informal support ; routine pharmacotherapy was provided by clinicians blind to group allocation . Patients were monitored weekly using self-report and mental state assessment s during admission and over the subsequent nine months . RESULTS Both groups showed a decline in positive symptoms but this was more marked in the CT group ( P < 0.001 ) . At 9 months 5 % of the CT group , v.56 % of the control group , showed moderate or severe residual symptoms . CONCLUSION CT appears to be a potent adjunct to pharmacotherapy and st and ard care for acute psychosis . Issues concerning internal and external validity of the study and opportunities for further research are discussed BACKGROUND The provision of early intervention services for people with psychosis is UK government policy , although evidence for benefit of such services is sparse . AIMS To evaluate the effects of a service providing specialised care for early psychosis ( the Lambeth Early Onset Team ) on clinical and social outcomes , and on service user satisfaction . METHOD One hundred and forty-four people with psychosis , presenting to mental health services for the first or second time ( if previously failed to engage in treatment ) , were r and omly allocated to care by the early onset team or to st and ard care . Information was obtained on symptoms , treatment adherence , social and vocational functioning , satisfaction and quality of life . Relapse and rehospitalisation data have been reported separately . RESULTS Outcomes for the participants treated by the early onset team were significantly better at 18 months for aspects of social and vocational functioning , satisfaction , quality of life and medication adherence . Symptom improvement did not significantly differ between the groups . CONCLUSIONS The provision of specialised care for early psychosis can achieve better outcomes . The study therefore provides support for current policy OBJECTIVE Identifying treatments to improve functioning and reduce negative symptoms in consumers with schizophrenia is of high public health significance . METHOD In this r and omized clinical trial , participants with schizophrenia or schizoaffective disorder ( N = 149 ) were r and omly assigned to cognitive behavioral social skills training ( CBSST ) or an active goal -focused supportive contact ( GFSC ) control condition . CBSST combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning and negative symptoms . GFSC was weekly supportive group therapy focused on setting and achieving functioning goals . Blind raters assessed functioning ( primary outcome : Independent Living Skills Survey [ ILSS ] ) , CBSST skill knowledge , positive and negative symptoms , depression , and defeatist performance attitudes . RESULTS In mixed-effects regression models in intent-to-treat analyses , CBSST skill knowledge , functioning , amotivation/asociality negative symptoms , and defeatist performance attitudes improved significantly more in CBSST relative to GFSC . In both treatment groups , comparable improvements were also found for positive symptoms and a performance-based measure of social competence . CONCLUSIONS The results suggest CBSST is an effective treatment to improve functioning and experiential negative symptoms in consumers with schizophrenia , and both CBSST and supportive group therapy actively focused on setting and achieving functioning goals can improve social competence and reduce positive symptoms The article reports the 2-year follow-up of patients suffering persistent symptoms of schizophrenia who entered a single blind r and omized controlled trial . Patients were r and omly allocated to cognitive-behavioral therapy ( CBT ) plus routine care ( RC ) , supportive counseling ( SC ) plus RC , or RC alone . Treatment took place over 3 months , and follow-up was made 12 and 24 months after treatment finished . Sixty-one patients were available to the 2-year follow-up and assessed for positive and negative symptoms and clinical improvement ; all of the 87 patients who entered the trial were assessed for relapse over the follow-up period . On all measures , patients who received RC alone did significantly worse at 2 years . There were no significant differences at 2 years between the CBT and SC groups OBJECTIVE Treatments for the cognitive impairments of schizophrenia are urgently needed . We developed and tested a 12-week , group-based , manualized , compensatory cognitive training intervention targeting prospect i ve memory , attention , learning/memory , and executive functioning . The intervention focused on compensatory strategies , such as calendar use , self-talk , note taking , and a 6-step problem-solving method , and did not require computers . METHOD In a r and omized controlled trial , 69 out patients with DSM-IV primary psychotic disorders were assigned to receive st and ard pharmacotherapy alone or compensatory cognitive training + st and ard pharmacotherapy for 12 weeks . Assessment s of neuropsychological performance and functional capacity ( primary outcomes ) and psychiatric symptom severity , quality of life , social skills performance , cognitive insight , and self-reported everyday functioning ( secondary outcomes ) were administered at baseline , posttreatment , and 3-month follow-up . Data were collected between September 2003 and August 2009 . RESULTS Hierarchical linear modeling analyses demonstrated significant compensatory cognitive training-associated effects on attention at follow-up ( P = .049 ) , verbal memory at posttreatment and follow-up ( P values ≤ .039 ) , and functional capacity ( University of California , San Diego Performance-based Skills Assessment ) at follow-up ( P = .004 ) . The compensatory cognitive training group also differentially improved in negative symptom severity at posttreatment and follow-up ( P values ≤ .025 ) and subjective quality of life at follow-up ( P = .002 ) . CONCLUSIONS Compensatory cognitive training , a low-tech , brief intervention , has the potential to improve not only cognitive performance but also functional skills , negative symptoms , and self-rated quality of life in people with psychosis . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01521026 Cognitive rehabilitation has shown beneficial effects on cognition in patients with schizophrenia , which may also help to improve negative symptoms due to overlapping pathophysiology between these two domains . To better underst and the possible relationship between these areas , we conducted an exploratory analysis of the effects of Cognitive Enhancement Therapy ( CET ) on negative symptoms . Early course schizophrenia out patients ( n=58 ) were r and omized to 2 years of CET or an Enriched Supportive Therapy ( EST ) control condition . Results revealed significant and medium-sized ( d=0.61 ) differential improvements favoring CET in overall negative symptoms , particularly social withdrawal , affective flattening , and motor retardation . Neurocognitive improvement was associated with reduced negative symptoms in CET , but not EST patients . No relationships were observed between improvements in emotion processing aspects of social cognition , as measured by the Mayer-Salovey-Caruso Emotional Intelligence Test , and negative symptoms . CET represents an effective cognitive rehabilitation intervention for schizophrenia that may also have benefits to negative symptoms . Future studies specifically design ed to examine negative symptoms during the course of cognitive rehabilitation are needed BACKGROUND Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia . Although the cumulative evidence is strong , early controlled trials showed method ological limitations . METHODS A r and omized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention . Both interventions were delivered by 2 experienced nurses who received regular supervision . Patients were assessed by blind raters at baseline , after treatment ( lasting up to 9 months ) , and at a 9-month follow-up evaluation . Patients continued to receive routine care throughout the study . An assessor blind to the patients ' treatment groups rated the technical quality of audiotaped sessions chosen at r and om . Analysis was by intention to treat . RESULTS Ninety patients received a mean of 19 individual treatment sessions over 9 months , with no significant between-group differences in treatment duration . Both interventions result ed in significant reductions in positive and negative symptoms and depression . At the 9-month follow-up evaluation , patients who had received cognitive therapy continued to improve , while those in the befriending group did not . These results were not attributable to changes in prescribed medication . CONCLUSION Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to st and ard antipsychotic drugs , with its efficacy sustained over 9 months of follow-up BACKGROUND The ACE project involved 62 participants with a first episode of psychosis r and omly assigned to either a cognitive behaviour therapy ( CBT ) intervention known as Active Cognitive Therapy for Early Psychosis ( ACE ) or a control condition known as Befriending . The study hypotheses were that : ( 1 ) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending ; ( 2 ) these improvements in symptoms and functioning would be sustained at a 1-year follow-up ; and ( 3 ) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up . METHOD Two therapists treated the participants across both conditions . Participants could not receive any more than 20 sessions within 14 weeks . Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning : at pretreatment , the middle of treatment , the end of treatment and at 1-year follow-up . An independent pair of raters assessed treatment integrity . RESULTS Both groups improved significantly over time . ACE significantly outperformed Befriending by improving functioning at mid-treatment , but it did not improve positive or negative symptoms . Past the mid-treatment assessment , Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up . CONCLUSIONS There is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger sample A motivation is a telling hallmark of negative symptomatology in schizophrenia , and it impacts nearly every facet of behavior , including inclination to attempt the difficult cognitive tasks involved in cognitive remediation therapy . Experiences of external reward , reinforcement , and hedonic anticipatory enjoyment are diminished in psychosis , so therapeutics which instead target intrinsic motivation for cognitive tasks may enhance task engagement , and subsequently , remediation outcome . We examined whether out patients could attain benefits from an intrinsically motivating instructional approach which ( a ) presents learning material s in a meaningful game-like context , ( b ) personalizes elements of the learning material s into themes of high interest value , and ( c ) offers choices so patients can increase their control over the learning process . We directly compared one learning method that incorporated the motivational paradigm into an arithmetic learning program against another method that carefully manipulated out the motivational variables in the same learning program . Fifty-seven subjects with schizophrenia or schizoaffective disorder were r and omly assigned to one of the two learning programs for 10 thirty-minute sessions while an intent-to-treat convenience sub sample ( n=15 ) was used to account for practice effect . Outcome measures were arithmetic learning , attention , motivation , self competency , and symptom severity . Results showed the motivational group ( a ) acquired more arithmetic skill , ( b ) possessed greater intrinsic motivation for the task , ( c ) reported greater feelings of self competency post-treatment , and ( d ) demonstrated better post-test attention . Interestingly , baseline perception of self competency was a significant predictor of post-test arithmetic scores . Results demonstrated that incorporating intrinsically motivating instructional techniques into a difficult cognitive task promoted greater learning of the material , higher levels of intrinsic motivation to attempt the dem and ing task , and greater feelings of self efficacy and achievement to learn OBJECTIVE Most research on the Illness Management and Recovery ( IMR ) program for people with severe mental illnesses has focused on individuals with stable symptoms living in the community , with less attention to persons being treated in an inpatient setting . We evaluated the feasibility and effects of an IMR program adapted for individuals with schizophrenia who were awaiting discharge into the community . METHOD A r and omized controlled trial was conducted at 2 hospitals in Taiwan to compare the adapted IMR program with treatment as usual ( TAU ) . Ninety-seven individuals with schizophrenia were r and omized to the adapted IMR program or TAU . Four outcome indicators including illness-management knowledge , attitudes toward medication , insight , and symptoms were assessed at baseline , posttreatment , and at a 1-month follow-up following discharge from the hospital . RESULTS Participants in the adapted IMR group showed significantly greater improvements at posttreatment and 1-month follow-up in illness-management knowledge , attitudes toward medication , insight , and negative symptoms on the Brief Psychiatric Rating Scale ( BPRS ) than individuals in the TAU group . There were no significant differences between the 2 groups on other subscales of the BPRS . CONCLUSIONS AND IMPLICATION S FOR PRACTICE This is the first controlled evaluation of a version of the IMR program in an East Asian culture , and the first to evaluate it in an acute care inpatient setting . Our findings support the feasibility and potential benefits of implementing an adapted IMR program , focused on the prevention of relapses and rehospitalizations , during the discharge period of an inpatient treatment stay to prepare individuals to reenter the community CONTEXT Intensive early treatment for first-episode psychosis has been shown to be effective . It is unknown if the positive effects are sustained for 5 years . OBJECTIVE To determine the long-term effects of an intensive early-intervention program ( OPUS ) for first-episode psychotic patients . DESIGN Single-blinded , r and omized , controlled clinical trial of 2 years of an intensive early-intervention program vs st and ard treatment . Follow-up periods were 2 and 5 years . SETTING Copenhagen Hospital Corporation and Psychiatric Hospital , Aarhus , Denmark . Patients A total of 547 patients with a first episode of psychosis . Of these , 369 patients were participating in a 2-year follow-up , and 301 were participating in a 5-year follow-up . A total of 547 patients were followed for 5 years . INTERVENTIONS Two years of an intensive early-intervention program vs st and ard treatment . The intensive early-intervention treatment consisted of assertive community treatment , family involvement , and social skills training . St and ard treatment offered contact with a community mental health center . MAIN OUTCOME MEASURES Psychotic and negative symptoms were recorded . Secondary outcome measures were use of services and social functioning . RESULTS Analysis was based on the principles of intention-to-treat . Assessment was blinded for previous treatment allocation . At the 5-year follow-up , the effect of treatment seen after 2 years ( psychotic dimension odds ratio [ OR ] , -0.32 ; 95 % confidence interval [ CI ] , -0.58 to -0.06 ; P = .02 ; negative dimension OR , -0.45 ; 95 % CI , -0.67 to -0.22 ; P = .001 ) had equalized between the treatment groups . A significantly smaller percentage of patients from the experimental group were living in supported housing ( 4 % vs 10 % , respectively ; OR , 2.3 ; 95 % CI , 1.1 - 4.8 ; P = .02 ) and were hospitalized fewer days ( mean , 149 vs 193 days ; mean difference , 44 days ; 95 % CI , 0.15 - 88.12 ; P = .05 ) during the 5-year period . CONCLUSIONS The intensive early-intervention program improved clinical outcome after 2 years , but the effects were not sustainable up to 5 years later . Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program BACKGROUND In order to improve the treatment of medication-resistant negative symptoms in schizophrenia , new interventions are needed . Neuropsychological considerations and older reports in the literature point towards a potential benefit of body-oriented psychological therapy ( BPT ) . This is the first r and omized controlled trial specifically design ed to test the effectiveness of manualized BPT on negative symptoms in chronic schizophrenia . METHOD Out- patients with DSM-IV continuous schizophrenia were r and omly allocated to either BPT ( n=24 ) or supportive counseling ( SC , n=21 ) . Both therapies were administered in small groups in addition to treatment as usual ( 20 sessions over 10 weeks ) . Changes in negative symptom scores on the Positive and Negative Symptom Scale ( PANSS ) between baseline , post-treatment and 4-month follow-up were taken as primary outcome criteria in an intention-to-treat analysis . RESULTS Patients receiving BPT attended more sessions and had significantly lower negative symptom scores after treatment ( PANSS negative , blunted affect , motor retardation ) . The differences held true at 4-month follow-up . Other aspects of psychopathology and subjective quality of life did not change significantly in either group . Treatment satisfaction and ratings of the therapeutic relationship were similar in both groups . CONCLUSIONS BPT may be an effective treatment for negative symptoms in patients with chronic schizophrenia . The findings should merit further trials with larger sample sizes and detailed studies to explore the therapeutic mechanisms involved Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment . Design Three arm , rater blinded , pragmatic , r and omised controlled trial . Setting Secondary care services across 15 sites in the United Kingdom . Participants 417 people aged 18 or over , who had a diagnosis of schizophrenia and provided written informed consent to take part in the study . Interventions Participants , stratified by site , were r and omised to 12 months of weekly group art therapy plus st and ard care , 12 months of weekly activity groups plus st and ard care , or st and ard care alone . Art therapy and activity groups had up to eight members and lasted for 90 minutes . In art therapy , members were given access to a range of art material s and encouraged to use these to express themselves freely . Members of activity groups were offered various activities that did not involve use of art or craft material s and were encouraged to collectively select those they wanted to pursue . Main outcome measures The primary outcomes were global functioning , measured using the global assessment of functioning scale , and mental health symptoms , measured using the positive and negative syndrome scale , 24 months after r and omisation . Main secondary outcomes were levels of group attendance , social functioning , and satisfaction with care at 12 and 24 months . Results 417 participants were assigned to either art therapy ( n=140 ) , activity groups ( n=140 ) , or st and ard care alone ( n=137 ) . Primary outcomes between the three study arms did not differ . The adjusted mean difference between art therapy and st and ard care at 24 months on the global assessment of functioning scale was −0.9 ( 95 % confidence interval −3.8 to 2.1 ) , and on the positive and negative syndrome scale was 0.7 ( −3.1 to 4.6 ) . Secondary outcomes did not differ between those referred to art therapy or those referred to st and ard care at 12 or 24 months . Conclusions Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning , mental health , or other health related outcomes . Trial registration Current Controlled Trials IS RCT N46150447 BACKGROUND Cognitive adaptation training ( CAT ) targets the adaptive behaviour of patients with schizophrenia and has shown promising results regarding the social aspects of psychosocial treatment . As yet , no reports have appeared on the use of CAT in combination with assertive community treatment ( ACT ) . Our purpose was to evaluate the effect of CAT in comparison with ACT , focusing on social functions ( primary outcome ) , symptoms , relapse , re-hospitalisation , and quality of life of out patients with schizophrenia . METHODS The trial was a parallel , r and omised , multicentre trial conducted in three centres treating patients with a first episode of schizophrenia disorder . A total of 62 out patients diagnosed as having schizophrenia were r and omly assigned to CAT+ACT or ACT alone . The CAT was conducted in the patient 's home and included instruction in prompting for specific actions . The treatment lasted for 6months , and the patients were assessed at baseline and at 6- and 9-month follow-ups . RESULTS The results of mixed-effects regression models indicated no significant differences between intervention group and control group at 6 and 9months in any outcome [ Global Assessment of Functioning at 6months ( p=0.32 ) and the Health of the Nation Outcome Scales social subscale at 6months ( p=0.30 ) ] . CONCLUSION The results from this trial differ from previous CAT trials because use of CAT showed no significant effects . However , the low number of participants may have been responsible for these results . Thus , additional studies are needed to determine whether the use of some elements of CAT can help to make ACT more economically effective Background There is increasing evidence indicating that the Community Re-entry Module ( CRM ) , a brief , structured instrument , could guide an effective intervention for patients with schizophrenia . This study evaluated the effectiveness of the Chinese version of the CRM with respect to improvement in psychiatric symptoms , social functioning as well as relapse and re-hospitalization rates in comparison with a supportive counseling ( SC ) intervention . Method Ninety-six out patients with DSM-IV schizophrenia were r and omly allocated to either CRM ( N=48 ) or an equally intensive intervention of SC ( N=48 ) . The CRM was composed of 16 one-hour sessions , which were conducted with groups of 6–8 patients on a twice-a-week schedule . The two groups received routine psychiatric outpatient care during the intervention . Participants were assessed on an intention-to-treat basis with the Positive and Negative Syndrome Scales ( PANSS ) , with the Social Disability Screening Schedule ( SDSS ) by two independent raters before and immediately after intervention , and at 6-month follow-up . The number of relapse and re-hospitalization were also documented . Results The CRM group significantly improved in terms of psychiatric symptoms and social functioning compared with the SC group . Rates of relapse and re-hospitalization in the CRM group were lower although the difference between the two groups was not statistically significant . Conclusions The study supports the feasibility and effectiveness of the Chinese version of the CRM as an effective psychosocial intervention for Chinese patients with schizophrenia to improve psychopathology , social functioning and relapse and re-hospitalization rates Background : Schizophrenia is a highly disabling illness . Previous studies have shown yoga to be a feasible add-on therapy in schizophrenia . Aims : The current study aim ed to test the efficacy of yoga as an add-on treatment in out patients with schizophrenia . Setting s and Design : The study done at a tertiary psychiatry center used a single blind r and omized controlled design with active control and waitlist groups . Material s and Methods : Consenting patients with schizophrenia were r and omized into yoga , exercise , or waitlist group . They continued to receive pharmacological therapy that was unchanged during the study . Patients in the yoga or exercise group were offered supervised daily procedures for one month . All patients were assessed by a blind rater at the start of the intervention and at the end of 4 months . Results : Kendall tau , a nonparametric statistical test , showed that significantly more patients in the yoga group improved in Positive and Negative Syndrome Scale ( PANSS ) negative and total PANSS scores as well as social functioning scores compared with the exercise and waitlist group . Odds ratio analysis showed that the likelihood of improvement in yoga group in terms of negative symptoms was about five times greater than either the exercise or waitlist groups . Conclusion : In schizophrenia patients with several years of illness and on stabilized pharmacological therapy , one-month training followed by three months of home practice s of yoga as an add-on treatment offered significant advantage over exercise or treatment as usual . Yoga holds promise as a complementary intervention in the management of schizophrenia We assessed the impact of humorous movies on psychopathology , anxiety , depression , anger , social functioning , insight , and therapeutic alliance in schizophrenia in patients . Twenty-nine psychiatric in patients in open wards participated in the study . The study group viewed humorous and the control group viewed neutral movies daily for 3 months . Participants were assessed before and after viewing movies with the Positive and Negative Symptom Scale , Calgary Depression Scale , the State-Trait Anxiety Inventory , the State-Trait Anger Expression Inventory-2 , the Multinomah Community Ability Scale , the Insight and Treatment Attitude Question naire , and the Working Alliance Inventory . Reduced levels of psychopathology , anger , anxiety , and depression symptoms and an improvement in social competence were revealed in the study group . No changes were observed in treatment insight or working alliance . Video films are a practical and cost-efficient means of entertainment that seem to have a positive effect on patient morale , mood , and mental status OBJECTIVES In schizophrenia , the ability to adaptively infer the thoughts and feelings of others ( i.e. , social cognition ) is strongly associated with community functioning . Research ers have design ed psychosocial interventions to improve social cognition with the aim of improving downstream social functioning . Social Cognition and Interaction Training ( SCIT ) is one such intervention . Previous research on SCIT has been promising , but has consisted largely of smaller trials with insufficient experimental control . DESIGN R and omized , controlled trial . METHODS The current article reports on a controlled trial of 66 adults with schizophrenia r and omized to receive either SCIT ( n = 33 ) , delivered in weekly group sessions , or treatment as usual ( n = 33 ) for 6 months . Participants completed assessment s of social cognition , social functioning , neurocognition and symptoms at baseline , post-treatment , and 3-month follow-up . RESULTS Primary analyses suggest that SCIT may improve social functioning , negative symptoms , and possibly hostile attributional bias . Post-hoc analyses suggest a dose-response effect . CONCLUSIONS Findings are discussed in the context of continuing to refine and improve social cognitive interventions for schizophrenia . PRACTITIONER POINTS Social cognitive intervention is a feasible and promising approach to improving social functioning among individuals with schizophrenia-spectrum disorders . Dose-response findings suggest that delivering social cognitive interventions with greater frequency may maximize their benefit to patients . Research on social cognitive interventions is still young and effects from well-controlled trials have been inconsistent . It is not yet clear which components of social cognitive training may be the key active ingredients The aim of this study was to determine whether occupational therapy ( OT ) can improve the interpersonal relationships and negative symptoms of hospitalized chronic schizophrenia patients with severe negative symptoms . Subjects were 38 patients with chronic schizophrenia . They were r and omly divided into an OT group and a control group . Patients in the OT group participated in cooking activities once a week for 15 weeks , while patients in the control group did not . During this period , both groups had the usual treatment except for the cooking activities . In interviews , the patient was asked to place a chair toward the interviewer ( a therapist ) . The angle and distance from the interviewer were taken as indicators of an ability to have interpersonal relationships . Negative symptoms were evaluated with the Scale for the Assessment of Negative Symptoms ( SANS ) . Patients who received OT were able to sit at the smaller angle and shorter distance from the interviewer than before OT ( p=0.015 and p=0.013 , respectively ) . The total SANS score was lower after OT than before OT ( p=0.033 ) . In the control group , the distance from the interviewer also decreased during the experimental period ( p=0.040 ) but the seating angle and the SANS scores did not change . The results suggest that OT can help to improve a relationship allowing the patient to face the therapist and that it might improve negative symptoms of schizophrenia BACKGROUND Overall results from Cognitive Remediation ( CR ) indicate robust and long-lasting effects with medium effect size on global cognition and functioning , and a small ES on symptoms present at post-treatment but not at follow-up . However , results are not the same in all CR therapies and in some cases no efficacy results are achieved . AIMS To develop an integrative intervention taking into account previous efficacious therapies . To evaluate the efficacy of our cognitive remediation group training : Problem Solving and Cognitive Flexibility training ( REPYFLEC ) , with the aim of improving cognition and functioning in schizophrenia patients . METHOD Participants with a diagnosis of schizophrenia or schizoaffective disorder ( n=62 ) were r and omized to 32 group sessions of REPYFLEC CR , or to 32 group sessions of activities without specific objectives and focused on leisure . In both groups the sessions were conducted twice a week . Functioning and psychiatric symptoms were measured at baseline ( week 0 ) and thereafter at 8 , 16 and 40 weeks . Cognition was measured at weeks 0 , 16 and 40 . Mixed Models were used to estimate statistical differences . RESULTS Patients in the cognitive remediation group demonstrated significant improvements in executive function , negative symptoms and functioning at post-treatment compared with patients in the control group . At 6-month follow-up , significant improvements in executive function and functioning remained . CONCLUSION These results apparently show that REPYFLEC works as cognitive remediation training , improving executive thinking and functioning outcomes compared with a control group BACKGROUND Meta-analyses support the efficacy of cognitive-behavioural therapy ( CBT ) for schizophrenia in western cultures . This study aim ed to compare the efficacy of CBT and supportive therapy ( ST ) for patients with schizophrenia in China . METHOD A multicentre r and omized controlled , single-blinded , parallel-group trial enrolled a sample of 192 patients with schizophrenia . All patients were offered 15 sessions of either CBT or ST over 24 weeks and followed up for an additional 60 weeks . All measures used were st and ardized instruments with good reliability and validity . The Positive and Negative Syndrome Scale ( PANSS ) was used to assess symptoms of schizophrenia . The Schedule for Assessing Insight ( SAI ) was used to assess patients ' insight and the Personal and Social Performance Scale ( PSP ) was used to assess their social functioning . RESULTS Effect-size analysis showed that patients made rapid improvements in all symptoms , insight and social functioning as measured by the PANSS , SAI and PSP at 12 and 24 weeks and maintained these improvements over the course of the study to 84 weeks . Patients in the CBT group showed significantly greater and more durable improvement in PANSS total score ( p = 0.045 , between-group d = 0.48 ) , positive symptoms ( p = 0.018 , between-group d = 0.42 ) and social functioning ( p = 0.037 , between-group d = 0.64 ) , with significant differences emerging after completion of therapy . CONCLUSIONS Both CBT and ST combined with medication had benefits on psychopathology , insight and social functioning of patients with schizophrenia . CBT was significantly more effective than ST on overall , positive symptoms and social functioning of patients with schizophrenia in the long term BACKGROUND Recent research progress showing the benefits of cognitive therapy in schizophrenia leaves the general psychiatrist unsure whether to attempt to use such techniques . AIMS To test whether cognitive-behavioural techniques are beneficial in the management of patients with schizophrenia in general psychiatric practice . METHOD A r and omised controlled study comparing the use of cognitive-behavioural techniques and befriending in schizophrenia . RESULTS Significant improvement in symptoms occurred in the group treated with cognitive-behavioural techniques but not in the befriending group . During the 6-month follow-up period the cognitive-behavioural group tended to have shorter periods in hospital . CONCLUSIONS General psychiatrists could help their patients with schizophrenia by using cognitive-behavioural techniques . Such techniques are well within the capability of general psychiatrists , but their application would involve more of the consultant 's time spent in direct contact with patients with psychoses BACKGROUND Evidence of the efficacy of cognitive-behavioral therapy ( CBT ) for schizophrenia is increasing . There are very few studies of effectiveness , especially in the medium term . OBJECTIVE To evaluate the durability of the effect of brief CBT provided by mental health nurses in community-based patients with schizophrenia ( diagnosed according to ICD-10 research criteria ) , using time to relapse as primary outcome and days hospitalized and occupational recovery as secondary outcomes at 24-month follow-up . METHOD A 2:1 r and omized trial , conducted from 1999 to 2003 , was performed to evaluate the effects of brief CBT delivered by mental health nurses trained over 10 days with ongoing supervision compared to treatment as usual ( TAU ) , with measurement performed by raters blind to treatment allocation . RESULTS 205 ( 79.8 % ) of 257 CBT patients and 125 ( 75.8 % ) of 165 TAU patients could be followed up at 24 months . Of 205 patients in the CBT group , 64 ( 31.2 % ) relapsed , versus 57 ( 45.6 % ) of 125 patients in the TAU group ( p = .02 ) . Patients rehospitalized from the CBT group spent a total of 6710 days in hospital ( mean = 32.7 days ) , while those from the TAU group were in patients for 6114 days ( mean = 48.9 days ) ( p < .05 ) . Twenty-one ( 10.2 % ) of 205 patients made an occupational recovery in the CBT group , and 17 ( 13.6 % ) of 125 , in the TAU group ( chi(2 ) test not significant ) . Mean time to relapse was 356.8 days ( SD = 241.9 days ) for the CBT group and 296.1 days ( SD = 215.7 days ) for the TAU group ( OR = 1.592 , 95 % CI = 1.038 to 2.441 , p = .033 ) . CONCLUSION Beneficial effects on relapse and rehospitalization following brief CBT delivered by mental health nurses in community-based patients with schizophrenia are maintained at 24-month follow-up . Occupational recovery is not improved by brief CBT Introduction : This study aim ed to evaluate the effectiveness of exercise and token-behavior therapy on the negative symptoms of schizophrenic patients . Objective : Comparison of the effectiveness of exercise and token-behavior therapy on the negative symptoms of schizophrenic patients . Methods : This research was a r and omized controlled clinical trial that was done on 45 schizophrenic patients , hospitalized in Rasht , Iran . Through systematic r and om allocation , the sample s were placed in one control and two intervention groups , 15 patients in each . To assess the negative symptoms , the scale for the assessment of negative symptoms ( SANS ) was used . The effect of the interventions used ( exercise and token-behavior therapy ) was studied by completing the relevant checklists before and after using the interventions , and then , by comparing it with that of the studied control group . In order to analyze the collected data , one way ANOVA and Bonferroni 's test and SPSS software were used . Results : Analyses showed that the token reinforcement approach was highly and significantly more effective than exercise for reducing the negative symptoms in schizophrenic patients ( –36 ± 7 vs. –21 ± 8 , respectively ; P<0.001 ) . Exercise was also shown to have a highly significant advantage over no therapy , in controls , to improve the negative symptoms in schizophrenic patients ( –25 ± 8 vs. 0.2 ± 1.08 , respectively ; P<0.001 ) . Conclusion : Both exercise and token-behavior therapies , along with drug treatment , are very effective in reducing the negative symptoms of schizophrenia ; but the impact of token therapy issignificantly higher BACKGROUND Cognitive remediation ( CR ) aims primarily to improve cognition and functional outcomes . However , a limited number of studies reported a positive effect on symptoms . This limited effect may be because the symptom clusters considered are too broad and heterogeneous . This study explores , for the first time , the effect of CR on five empirically defined symptom dimensions of schizophrenia . METHOD Participants were patients with schizophrenia taking part in a r and omised controlled trial comparing CR plus treatment as usual ( CR , N=43 ) to treatment as usual ( TAU , N=42 ) . All participants were assessed at baseline and 14-weeks ( i.e. at the conclusion of treatment for the CR group ) with the Positive and Negative Symptoms Scale ( PANSS ) . Five symptom dimensions were derived from the PANSS scores : Positive ( POS ) , Negative ( NEG ) , Disorganised ( DIS ) , Excited ( EXC ) and Emotional Distressed ( EMD ) . RESULTS After CR , the therapy group had a significant reduction in DIS and NEG symptom dimensions compared to the TAU group . The traditional PANSS factors showed no effect of CR on symptoms . CONCLUSION CR can have not only a positive effect on disorganisation but also on negative symptoms . Using detailed symptom dimensions can characterise more accurately the effect of CR on symptom of schizophrenia OBJECTIVES To examine the effects of a group music therapy on psychiatric symptoms and depression for patient with schizophrenia in a psychiatric nursing home . SUBJECTS AND METHODS Eighty patients with schizophrenia were r and omly assigned to a music intervention group ( MIG ) or usual care group ( UCG ) . Both groups received similar medical and routine care . The MIG received a 60-min group music therapy twice a week , a total of ten sessions . The UAG only received the usual care with no music therapy . Psychiatric symptoms and depression assessment s were conducted using the positive and negative syndrome scale and the depression scale for schizophrenia at baseline , the posttest , and at a 3-month follow-up . RESULTS Thirty-eight patients in the MIG and 42 in the UCG completed the study . After 10 sessions of group music therapy , the groups showed statistically significant differences in psychiatric symptoms ( p<.05 ) and depression status ( p<.05 ) . CONCLUSION Group music therapy is an economical and easily implemented method of improving depression and psychiatric symptoms in patients with schizophrenia Cognitive Adaptation Training ( CAT ) improves functional outcomes in schizophrenia out patients living in the United States . The effectiveness of CAT for patients living outside the US as well as for long-term hospitalized patients remains to be determined . In addition , it has not yet been studied whether CAT can be successful if patients receive the treatment from psychiatric nurses . This pilot study investigated the effectiveness and feasibility of CAT as a nursing intervention in the Netherl and s. Thirty schizophrenia patients ( long-term hospitalized patients : 63 % ) participated in this study . Sixteen patients received treatment as usual (TAU)+CAT , and fourteen patients received TAU . Patients in CAT participated in the treatment for eight months , consisting of weekly home-visits by a psychiatric nurse , supervised by a psychologist . After eight months , CAT interventions were integrated in the usual treatment . Outcome measures were the Multnomah Community Ability Scale ( MCAS ) , the Social and Occupational Functioning Scale ( SOFAS ) , and the Negative Symptom Assessment -Motivation subscale ( NSA-M ) . For in patients , work-related activities were also tracked for 16 months after baseline . Patients receiving TAU+CAT had better scores on the MCAS ( trend ) , compared to TAU patients . Moreover , in patients ' work-related activities increased in TAU+CAT , relative to TAU in patients , reaching significance after ten months . Improvements on the SOFAS and NSA-M were not significant . These results indicate that CAT as a nursing intervention may improve outcomes in patients with schizophrenia living in the Netherl and s , including long-term hospitalized patients . However , since the current study was design ed for exploratory purpose s , larger r and omized controlled studies are needed to confirm our results and to investigate the long-term effects of CAT as a nursing intervention systematic ally OBJECTIVE Outcomes for negative symptoms over a one-year period were examined in two groups of patients , one receiving psychoeducational multiple-family group treatment and one receiving st and ard care . METHODS A total of 63 out patients , ages 18 to 45 years , with DSM-IV diagnoses of schizophrenic disorders were r and omly assigned to st and ard care or multiple-family group psychoeducation treatment at a large mental health center in Spokane , Washington . Treatment assignment was stratified by whether patients were taking typical or atypical antipsychotic medications . Negative symptom status was monitored monthly for one year by raters blind to group assignment and measured as a composite of five symptoms using the Modified Scale for the Assessment of Negative Symptoms . RESULTS When the analysis controlled for baseline negative symptoms , participants in the multiple-family group experienced significantly reduced negative symptoms compared with those receiving st and ard care . Taking atypical antipsychotic medication or having a diagnosis of substance abuse was not associated with the severity of negative symptoms . An additional analysis of the five individual negative symptoms indicated small but consistent group differences on all dimensions except inattention . Negative symptoms were significantly correlated with relapse to acute illness but not with outpatient or inpatient service use . CONCLUSIONS The study demonstrated that a psychoeducational multiple-family group intervention was more effective than st and ard care in managing negative symptoms over a 12-month period . The results are particularly relevant because negative symptoms are associated with relapse , poor social and occupational functioning , cognitive impairment , and lower subjective quality of life OBJECTIVES The efficacy of cognitive remediation interventions in schizophrenia has been demonstrated in several experimental studies . However , the effectiveness of such treatments in the usual setting of care of schizophrenia and a direct comparison of different modalities of interventions have not been systematic ally analyzed . The aim of the study was to assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy ( IPT-cog ) and of a computer-assisted cognitive remediation ( CACR ) method on symptomatological , neuropsychological and functional outcome measures in schizophrenia . METHODS Ninety patients with schizophrenia were assigned to IPT-cog , CACR or usual rehabilitative interventions ( REHAB ) in a naturalistic setting of care . Clinical , neuropsychological , and functional outcome variables were assessed at baseline and after 24 weeks of treatment . RESULTS Both the IPT-cog and CACR groups improved more than the comparison group with respect to all outcome variables . The more responsive cognitive domains were speed of processing and working memory . The effectiveness of the 2 remediation methods on the outcome dimensions considered was comparable . However , IPT-cog , but not CACR , was more effective than REHAB on speed of processing , and the CACR group had better outcome than both the REHAB and the IPT-cog groups when the Health of the Nation Outcome Scale was considered . Few correlations between neurocognitive and functional outcome changes were found . CONCLUSIONS The study demonstrates the effectiveness , although nongeneralized , of IPT-cog and CACR in schizophrenia when applied within a psychiatric and psychosocial treatment regimen representative of the usual setting and modality of care , with no evident superiority of any of the methods , and indicates that the changes in functional outcome during treatment are modestly mediated by improvement in specific cognitive domains Peters E , L and au S , McCrone P , Cooke M , Fisher P , Steel C , Evans R , Carswell K , Dawson K , Williams S , Howard A , Kuipers E. A r and omised controlled trial of cognitive behaviour therapy for psychosis in a routine clinical service Achieving social functioning and achieving social competence are two main objectives of psychosocial interventions for people suffering from schizophrenia . The present preliminary study presents a novel approach of social skills training ( SST ) based on the proposals of Kopelowicz et al. ( Kopelowicz , A. , Liberman , R. P. , and Zarate , R. , 2006 . Schizophr . Bull . 32 ( 1 ) : S12 - 23 ) that link the treatment to seven specific target behaviours : social perception , social information processing , responding and sending skills , affiliative skills , interactional skills , and behaviour governed by social norms . Thirty-one stabilised out patients were r and omly assigned to one of two groups , SST ( n=13 ) or treatment-as-usual ( n=18 ) ( TAU ; case management , medication adherence , psychotherapy , leisure engagement , and family support ) and were assessed at baseline in cognitive performance , clinical symptomatology , social cognition , and psychosocial functioning . These outcomes were evaluated across post-treatment and at the 6-month follow-up appointment . SST subjects showed improvements in psychopathology , social discomfort , social cognition ( self-regulation statements during interactions ) , social withdrawal , interpersonal communication , and quality of life compared with the TAU group . At the 6-month follow-up , results were maintained for negative symptoms , social discomfort , and some functioning outcomes . Neuropsychological variables were also examined , as mediators of benefit from skills training . Results support the efficacy of the brief SST for out patients with schizophrenia and show the need to implement empirically supported interventions in mental health services to enhance patients ' social functioning and quality of life Meta-analyses of r and omized controlled trials support the efficacy of cognitive behavioral therapy ( CBT ) in the treatment of symptoms of schizophrenia refractory to antipsychotic medication . This article addresses the issue of medium term durability . A five-year follow-up was undertaken of a sample of 90 subjects who participated in a r and omized controlled trial of CBT and befriending ( BF ) . Patients received routine care throughout the trial and the follow-up period . Intention to treat multivariate analysis was performed by an independent statistician following multiple imputation of missing data . Fifty-nine out of ninety patients were followed up at 5 years ( CBT=31 , BF=28 ) . In comparison to BF and usual treatment , CBT showed evidence of a significantly greater and more durable effect on overall symptom severity ( NNT=10.36 , CI -10.21 , 10.51 ) and level of negative symptoms ( NNT=5.22 , CI -5.06 -5.37 ) . No difference was found between CBT and BF on either overall symptoms of schizophrenia or depression . The initial cost of an adjunctive course of CBT for individuals with medication refractory schizophrenia may be justified in light of symptomatic benefits that persist over the medium term A rehabilitative coping skills module employing problem solving and cognitive behavioral therapy and an experimental repeated-measure design was tested on 55 r and omly selected persons severely h and icapped by schizophrenia , most of whom had lived almost half of their lives in psychiatric wards . Unlike the control group of 44 comparable schizophrenics , the experimental group exhibited a significant decrease in delusions and increase in self-esteem , and maintained hygiene levels OBJECTIVE Many individuals diagnosed with schizophrenia have significant neurocognitive deficits , especially in the areas of attention , memory , and executive function . These deficits may exacerbate patients ' psychiatric symptoms . Cognitive remediation has shown efficacy in improving neurocognitive functioning and may lead to amelioration of psychiatric symptoms in persons with schizophrenia . METHOD Forty-two schizophrenic in patients were r and omly assigned to either a cognitive remediation group ( n=21 ) or a control group ( n=21 ) and were assessed using a neuropsychological battery and symptom scales for depression , anxiety , and positive and negative symptoms of schizophrenia at baseline and after two months of participation in a cognitive remediation program . RESULTS The intervention group showed significant improvements in neuropsychological functioning , depression and negative symptoms of schizophrenia after the intervention compared to the control group . CONCLUSION Results of the study provide support for cognitive remediation as an efficacious intervention to improve neurocognitive functioning and decrease psychiatric symptoms of schizophrenia Thirty-four-day treatment program clients diagnosed with schizophrenia or schizoaffective disorder were r and omly assigned to a computer-assisted cognitive rehabilitation ( CACR ) group or a wait-list Control group . CACR clients received 16 CACR sessions over an 8-week period . Measures of cognitive functioning , negative symptoms and self-esteem were administered at the beginning and end of this period . CACR clients showed greater improvement in cognitive functioning ( verbal memory and attention ) and negative symptoms . Symptom reduction was not mediated by raised self-esteem . CACR 's effects may go beyond cognitive remediation to include some of the most disabling and refractory clinical features of schizophrenia This study examined the relationship of the therapeutic alliance to the treatment course and outcome of 143 patients with nonchronic schizophrenia . Results showed that patients who formed good alliances with their therapists within the first 6 months of treatment were significantly more likely to remain in psychotherapy , comply with their prescribed medication regimens , and achieve better outcomes after 2 years , with less medication , than patients who did not . These results underscored the prognostic value of assessing the alliance and the need to identify factors that contribute to its development and maintenance with schizophrenic patients OBJECTIVE The primary aim of this pilot study was to evaluate the possible therapeutic effects of a 10-session humor intervention program in improving rehabilitative outcomes and the effects of the intervention on patients ' sense of humor among patients with schizophrenia . METHOD Thirty subjects were r and omly assigned into either the intervention ( humor skill training ) group ( n = 15 ) or the control ( doing h and work ) group ( n = 15 ) . The results were analyzed using descriptive statistics , t-tests and ANOVA . FINDINGS Repeated measures analysis of variance ( ANOVA ) tests were conducted to examine the differences across conditions and time . A group by time interaction effect was observed on all of the outcomes , except positive symptoms of PANSS . The time main effect was also significant on the total score ( p < 0.005 ) and the negative symptoms score ( p < 0.001 ) of the PANSS . CONCLUSIONS The implementation of humor skill training in a mental health service can improve rehabilitative outcomes and sense of humor for schizophrenia patients who were in the rehabilitation stage Cognitive Remediation Therapy ( CRT ) is a novel rehabilitation approach design ed to improve neurocognitive abilities such as attention , memory and executive functioning . The aim of the present study is to evaluate the effect of CRT on neurocognition , and secondarily on symptomatology and psychosocial functioning . Cognitive Behavioural Therapy ( CBT ) was used as a control condition because it aims to improve emotional problems and positive symptoms , focusing on modification of maladaptive beliefs and schemas , but neurocognition is not targeted . A total of 40 chronic patients with DSM-IV schizophrenia disorder were r and omly assigned for 4 months to one of two treatment groups : CRT or CBT . Repeated assessment s were conducted before and after the treatments and at the end of a follow-up period of 6 months . Additionally , a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under st and ard medication without any kind of psychological treatment . Results showed that CRT produced an overall improvement on neurocognition ( Mean effect size=0.5 ) , particularly in verbal and nonverbal memory , and executive function . CBT showed the expected treatment effect on general psychopathology ( anxiety and depression ) but produced only a slight non-specific improvement in neurocognition ( Working Memory ) . Furthermore , patients receiving CRT showed improvement in social functioning , demonstrating that cognitive improvements are clinical ly meaningful . These gains were still present at the 6 month follow-up OBJECTIVES There has been limited study of therapeutic yoga as a complementary treatment for schizophrenia . This study investigates the effects of a Yoga Therapy program on symptomatology and quality of life in adults with schizophrenia in a state psychiatric facility . METHODS In a r and omized , controlled pilot study , 18 clinical ly stable patients ( 12 men and 6 women ) with schizophrenia ( mean age=42±13.5 ) were r and omized to an 8-week Yoga Therapy program ( YT ) and a Waitlist group ( WL ) . YT intervention included yoga postures , breathing exercises , and relaxation . At baseline and at 8 weeks , symptomatology was measured using the Positive and Negative Syndrome Scale ( PANSS ) . Secondary efficacy outcomes were measured with the World Health Organization Quality of Life BREF question naire ( WHOQOL-BREF ) . RESULTS The YT group obtained significant improvements in positive and negative symptoms of schizophrenia symptoms compared to WL , including PANSS scores on positive syndrome ( t=-2.64 , p=0.02 ) , negative syndrome ( t=-3.04 , p<0.01 ) , general psychopathology ( t=-3.74 , p<0.00 ) , activation ( t=-2.29 , p<0.04 ) , paranoia ( t=-2.89 , p<0.01 ) , and depression subscales ( t=-2.62 , p<0.02 ) . PANSS total scores also decreased for the YT group ( t=-4.54 , p<0.00 ) . YT had improved perceived quality of life in physical ( t=2.38 , p<0.04 ) and psychologic domains ( t=2.88 , p<0.01 ) . CONCLUSIONS Adults with schizophrenia being treated in a state psychiatric facility who participated in an 8-week therapeutic yoga program showed significant improvements in psychopathology and quality of life compared with controls . The findings of this study need to be confirmed in larger , more sufficiently powered studies with active control groups Seventy-six in- patients who had the residual subtype of schizophrenia were r and omly assigned to a treatment group or a control group . Both groups received st and ard medication as prescribed by their treating physicians , but the treatment group also received a one-month course of music therapy that included both passive listening to music and active participation in the singing of popular songs with other patients . Outcome was evaluated by four nurses using Chinese versions of the Scale for Assessment of Negative Symptoms and the in-patient version of the World Health Organization 's Disability Assessment Scale . Music therapy significantly diminished patients ' negative symptoms , increased their ability to converse with others , reduced their social isolation , and increased their level of interest in external events . As music therapy has no side-effects and is relatively inexpensive , it merits further evaluation and wider application Psychosocial functioning impairment is recognized as a core feature of schizophrenia . Numerous studies have assessed the process that may underlie this impairment . In the last years , one of these processes that has been studied more is social cognition , which has been proposed as a mediator variable between neurocognition and functional outcome . Social cognition includes the subdomains of emotion recognition and social perception , and in recent years several authors have developed diverse training programs in these areas . The purpose of the present article is to assess the efficacy of the Social Cognition Training Program , a program that includes emotion recognition training and social perception training . The sample was made up of 14 out patients with a diagnosis of schizophrenia according to CIE-10 criteria , r and omly divided into two groups : experimental and control . All patients were assessed before and after the training program . Cognitive and psychopathological variables , social functioning , emotion recognition and social perception performance were assessed . Results suggest improvement in social perception and interpretation in the experimental group , in comparison with the control group , but not in emotion recognition . No significant correlations were obtained between social cognition training and other variables tested Clinical studies on cognitive behavioral therapy ( CBT ) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon . However , those studies are necessary to assess the efficacy of CBT on negative symptoms . This article first gives an overview of CBT on negative symptoms and discusses the method ological problems of selecting an adequate control group . Furthermore , the article describes a clinical study ( the TONES- Study , IS RCT N 25455020 ) , which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms . This multicenter r and omized clinical trial comparing CBT with cognitive remediation ( CR ) for control of nonspecific effects is depicted in detail . In our trial , schizophrenia patients ( n = 198 ) participated in manualized individual outpatient treatments . Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale , analyzed with multilevel linear mixed models . Patients in both groups moderately improved regarding the primary endpoint . However , against expectation , there was no difference between the groups after treatment in the intention to treat as well as in the per- protocol analysis . In conclusion , psychotherapeutic intervention may be useful for the reduction of negative symptoms . However , there is no indication for specific effects of CBT compared with CR This paper discusses the effectiveness of an in-patient rehabilitation programme administered by nurses that combines life skills training , active encouragement , and a token economy . Fifty-two chronic schizophrenic patients with prominent negative symptoms who had been continuously in hospital for at least a year were r and omly assigned to the experimental or control group . The training and associated reinforcement schedule were administered daily to experimental subjects by two specially trained rehabilitation nurses . Control subjects did not receive training or reinforcement but were individually asked to perform the same daily tasks and participate in the same activities as the experimental-group subjects . Patients in both groups received their previous dosage of medication throughout the trial . After three months the severity of negative symptoms , as assessed by blind evaluators , decreased in both groups of subjects , but the improvement in the experimental group was much greater than that in the control group . These findings demonstrate the efficacy of behavioural interventions for chronic schizophrenic in- patients in China and highlight the importance of changing the role of Chinese psychiatric nurses from that of custodians who control patients ' behaviour to that of therapists who provide psychological and behavioural treatment Cognitive remediation has proven efficacy for improving neurocognition in people with schizophrenia . The current study evaluated the benefits of cognitive remediation on neurocognition , functioning , psychotic symptoms , and aggression in a sample of forensic and mental health patients . Care recipients with schizophrenia or schizoaffective disorder ( N = 78 ) receiving services in the forensic and mental health units of a state hospital were r and omized to participate in cognitive remediation versus computer games control activities . Participants ' neurocognition , functional capacity , experiential recovery , psychotic symptoms , and aggression incidents were assessed at baseline and posttreatment . Cognitive remediation was associated with improvements in several neurocognitive domains and circumscribed domains of functional capacity . People assigned to cognitive remediation experiences greater reductions in negative symptoms , agitation/excitement , and verbal and physical aggression . In addition to improving neurocognition in long-term hospitalized forensic and mental health patients , cognitive remediation may enhance efforts at reducing negative symptoms , emotion dysregulation , and aggression incidents . Forensic setting s may represent a new frontier for the clinical dissemination of cognitive remediation OBJECTIVE The study compared the effects of social skills training and social milieu treatment on symptoms of schizophrenia , particularly on negative symptoms . METHODS Thirty-three patients aged 18 to 55 years with a diagnosis of schizophrenia were r and omly assigned to a nine-week program of social skills training or social milieu treatment . Patients were assessed at three- , six- , and nine-week intervals during treatment and at follow-up using the Positive and Negative Syndrome Scale ( PANSS ) , which measured both positive and negative symptoms of schizophrenia and general psychopathology . RESULTS Fifteen patients completed social skills training , and 13 completed social milieu treatment . Comparison of PANSS scores at different assessment times showed that both treatments were effective in reducing symptoms , but social skills training appeared to be more effective in reducing negative symptoms . No differences were found between treatment groups in relapse rates or in symptom measures at three-month follow-up . However , six-month follow-up data available only for the social skills training group showed that improvement in negative symptoms had begun to decline . CONCLUSIONS Psychosocial approaches are a necessary component in the treatment of patients with schizophrenia , and social skills training appears to be particularly helpful . The gradual decline in improvement in negative symptoms at six-month follow-up suggests the need for more extended treatment Individual-level cognitive remediation therapy ( CRT ) has been shown to be effective for cognitive improvement and social function amelioration . Here , we aim ed to test the efficacy of group-based CRT in Chinese subjects with schizophrenia . One-hundred and four in patients were r and omly assigned to either 40 sessions of small-group CRT therapy or therapeutic contact-matched Musical and Dancing Therapy ( MDT ) . Cognitive and social functioning , as well as clinical symptoms , were evaluated over the course of treatment . Specifically , cognitive function was evaluated using a battery of cognitive measurements , clinical symptoms were evaluated using the Positive and Negative Syndrome Scale , and social function was evaluated using the Nurse 's Observation Scale for Inpatient Evaluation-30 . All patients were evaluated pre- and post-treatment . Forty-four individuals in the CRT group and 46 in the MDT group completed all of the planned treatments and analyses . Cognitive functions , especially cognitive flexibility and memory , showed significant improvement in the CRT group over the course of the study . The MDT group also showed improvement in several cognitive flexibility assessment s , but the degree of improvement was significantly greater in the CRT group . Several social-function factors exhibited a significant improvement in the CRT group , but not in the MDT group . Cognitive function improvement correlated positively with social function without predicting social function change . We conclude that group-based CRT is an effective and promising therapy Cognitive remediation improves cognition in patients with schizophrenia , but its effect on other relevant factors such as negative symptoms and functional outcome has not been extensively studied . In this hospital-based study , 84 in patients with chronic schizophrenia were recruited from Alava Hospital ( Spain ) . All of the subjects underwent a baseline and a 3-month assessment that examined neurocognition , clinical symptoms , insight , and functional outcome according to the Global Assessment of Functioning ( GAF ) scale and Disability Assessment Schedule from World Health Organization ( DAS-WHO ) . In addition to receiving st and ard treatment , patients were r and omly assigned either to receive neuropsychological rehabilitation ( REHACOP ) or to a control group . REHACOP is an integrative program that taps all basic cognitive functions . The program included experts ' latest suggestions about positive feedback and activities of daily living in the patients ' environment . The REHACOP group showed significantly greater improvements at 3 months in the areas of neurocognition , negative symptoms , disorganization , and emotional distress compared with the control group ( Cohen 's effect size for these changes ranged from d = 0.47 for emotional distress to d = 0.58 for disorganization symptoms ) . The REHACOP group also improved significantly in both the GAF ( d = 0.61 ) and DAS-WHO total scores ( d = 0.57 ) . Specifically , the patients showed significant improvement in vocational outcomes ( d = 0.47 ) , family contact ( d = 0.50 ) , and social competence ( d = 0.56 ) . In conclusion , neuropsychological rehabilitation may be useful for the reduction of negative symptoms and functional disability in schizophrenia . These findings support the integration of neuropsychological rehabilitation into st and ard treatment programs for patients with schizophrenia The purpose of this study was to examine the effects of 10 weeks of physical exercises programme on mental states and quality of life ( QOL ) of individuals with schizophrenia . The study involved 30 in patients or out patients with schizophrenia who were assigned r and omly into aerobic exercise ( n = 15 ) group and control ( n = 15 ) group , participated to the study voluntarily . There were no personal differences such as age , gender , disorder duration , medication use between the both groups . An aerobic exercise programme was applied to the subject group , the periods of 10 weeks as 3 days in a week . Data were collected by using the Brief Symptom Inventory , the Scale for the Assessment of Positive Symptoms , the Scale for the Assessment of Negative Symptoms and to the both group before and after the exercise programme . After the 10-week aerobic exercise programmes the subjects in the exercise programme showed significantly decreases in the Scale for the Assessment of Positive Symptoms , the Scale for the Assessment of Negative Symptoms and the Brief Symptom Inventory points and their World Health Organization Quality of Life Scale-Turkish Version points were increased than controls . These results suggest that mild to moderate aerobic exercise is an effective programme for decreasing psychiatric symptoms and for increasing QOL in patients with schizophrenia OBJECTIVE This report describes 1- , 2- , and 3-year outcomes of a combined psychosocial skills training and preventive healthcare intervention ( Helping Older People Experience Success [ HOPES ] ) for older persons with serious mental illness . METHODS A r and omized controlled trial compared HOPES with treatment as usual ( TAU ) for 183 older adults ( age ≥ 50 years [ mean age : 60.2 ] ) with serious mental illness ( 28 % schizophrenia , 28 % schizoaffective disorder , 20 % bipolar disorder , 24 % major depression ) from two community mental health centers in Boston , Massachusetts , and one in Nashua , New Hampshire . HOPES comprised 12 months of weekly skills training classes , twice-monthly community practice trips , and monthly nurse preventive healthcare visits , followed by a 1-year maintenance phase of monthly sessions . Blinded evaluations of functioning , symptoms , and service use were conducted at baseline and at a 1-year ( end of the intensive phase ) , 2-year ( end of the maintenance phase ) , and 3-year ( 12 months after the intervention ) follow-up . RESULTS HOPES compared with TAU was associated with improved community living skills and functioning , greater self-efficacy , lower overall psychiatric and negative symptoms , greater acquisition of preventive healthcare ( more frequent eye exams , visual acuity , hearing tests , mammograms , and Pap smears ) , and nearly twice the rate of completed advance directives . No differences were found for medical severity , number of medical conditions , subjective health status , or acute service use at the 3-year follow-up . CONCLUSION Skills training and nurse facilitated preventive healthcare for older adults with serious mental illness was associated with sustained long-term improvement in functioning , symptoms , self-efficacy , preventive healthcare screening , and advance care planning This study aim ed at determining the effectiveness of group cognitive behavior therapy ( CBT ) for recent onset psychosis in comparison with a recognized intervention for individuals with severe mental illness – social skills training . One hundred twenty-nine participants took part in a single-blind r and omized controlled trial with repeated measures ( baseline , 3 months , and 9 months ) . Participants were r and omized to 1 of 3 conditions : group CBT , group social skills training for symptom management , or a wait-list control group . Both interventions were delivered by mental health staff with minimal training . Both treatments result ed in improvements on positive and negative symptoms compared with the wait-list control group , with the CBT group having significant effects over time on overall symptoms , and post-treatment effects on self-esteem , and active coping skills compared with the wait-list control group and lower drop-out rates than the skills training group . Therapist fidelity was adequate for both treatment conditions . Group CBT for psychosis is a promising intervention for individuals with recent onset of psychosis and their mental health professionals AIM People with schizophrenia tend to experience difficulties in social and cognitive function , self-care , residual negative symptoms , high rates of unemployment , and social exclusion . Occupational therapy has contributed to the treatment and rehabilitation of people with severe mental health problems . Therefore , this study investigated the effects of occupational therapy on symptoms of patients with schizophrenia . METHODS This survey was an experimental study in which positive and negative symptoms of patients with schizophrenia were assessed with a scale for the assessment of positive and negative symptoms ( SANS , SAPS , respectively ) . The study was conducted in Sina Hospital , Shahrekord , Iran . The sample s consisted of patients with schizophrenia who were divided r and omly into intervention and usual treatment groups ( 30 patients in each group ) . The occupational therapy was performed in the intervention group for 18 h/week for 6 months . SANS and SAPS were assessed at the beginning and after 6 months of treatment . RESULTS The groups were homogeneous in demographic variables , SANS and SAPS scores at baseline . The occupational therapy group showed significant improvement in the total score for the SANS and SAPS at 6 months ( P<0.001 ) , but the control group did not show any significant improvement . CONCLUSION The results of this study indicated that occupational therapy combined with medications can improve the symptoms of schizophrenia The experience of psychosis can lead to depression , anxiety and fear . Acceptance and Commitment Therapy ( ACT ) facilitates individuals to accept difficult mental experiences and behave in ways that are consistent with personally held values . This study was a single ( rater ) blind pilot r and omised controlled trial of ACT for emotional dysfunction following psychosis . Twenty-seven participants with psychosis were r and omised to either : ten sessions of ACT plus treatment as usual ( TAU ) or TAU alone . The Hospital Anxiety and Depression Scale , Positive and Negative Syndrome Scale , Acceptance and Action Question naire , Kentucky Inventory of Mindfulness Skills and Working Alliance Inventory were used . Individuals were assessed at baseline and 3 months post-baseline . The individuals r and omised to receive ACT found the intervention acceptable . A significantly greater proportion of the ACT group changed from being depressed at time of entry into the study to not being depressed at follow-up . The ACT group showed a significantly greater increase in mindfulness skills and reduction in negative symptoms . Results indicated that individuals r and omised to ACT had significantly fewer crisis contacts over the study . Changes in mindfulness skills correlated positively with changes in depression . ACT appears to offer promise in reducing negative symptoms , depression and crisis contacts in psychosis Context : The efficacy of yoga as an intervention for in- patients with psychosis is as yet unknown ; although , previous studies have shown efficacy in stabilized out- patients with schizophrenia . Aim : This study aim ed to compare the effect of add-on yoga therapy or physical exercise along with st and ard pharmacotherapy in the treatment of in- patients with psychosis . Setting s and Design : This study was performed in an in-patient setting using a r and omized controlled single blind design . Material s and Methods : A total of 88 consenting in- patients with psychosis were r and omized into yoga therapy group ( n=44 ) and physical exercise group ( n=44 ) . Sixty patients completed the study period of 1½ months . Patients who completed in the yoga group ( n=35 ) and in the exercise group ( n=25 ) were similar on the demographic profile , illness parameters and psychopathology scores at baseline . Results : The two treatment groups were not different on the clinical syndrome scores at the end of 2 weeks . At the end of 6 weeks , patients in the yoga group however had lower mean scores on Clinical Global Impression Severity ( CGIS ) , Positive and Negative Syndrome Scale ( total and general psychopathology subscale ) and Hamilton Depression Rating Scale ( HDRS ) ( P<0.05 ) . Repeated measure analysis of variance detected an advantage for yoga over exercise in reducing the clinical CGIS and HDRS scores . Conclusion : Adding yoga intervention to st and ard pharmacological treatment is feasible and may be beneficial even in the early and acute stage of psychosis Background : Music therapy ( MT ) has been shown to be efficacious for mental health care clients with various disorders such as schizophrenia , depression and substance abuse . Referral to MT in clinical practice is often based on other factors than diagnosis . We aim ed to examine the effectiveness of re source -oriented MT for mental health care clients with low motivation for other therapies . Method : This was a pragmatic parallel trial . In specialised centres in Norway , Austria and Australia , 144 adults with non-organic mental disorders and low therapy motivation were r and omised to 3 months of biweekly individual , re source -oriented MT plus treatment as usual ( TAU ) or TAU alone . TAU was typically intensive ( 71 % were in patients ) and included the best combination of therapies available for each participant , excluding MT . Blinded assessment s of the Scale for the Assessment of Negative Symptoms ( SANS ) and 15 secondary outcomes were collected before r and omisation and after 1 , 3 and 9 months . Changes were analysed on an intention-to-treat basis using generalised estimating equations in longitudinal linear models , controlling for diagnosis , site and time point . Results : MT was superior to TAU for total negative symptoms ( SANS , d = 0.54 , p < 0.001 ) as well as functioning , clinical global impressions , social avoidance through music , and vitality ( all p < 0.01 ) . Conclusion : Individual MT as conducted in routine practice is an effective addition to usual care for mental health care clients with low motivation OBJECTIVE R and omized controlled trials have attested the efficacy of cognitive behavioral therapy ( CBT ) in reducing psychotic symptoms . Now , studies are needed to investigate its effectiveness in routine clinical practice setting s. METHOD Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were r and omized to a specialized cognitive behavioral intervention for psychosis ( CBTp ; n = 40 ) or a wait list ( n = 40 ) . The CBTp group was assessed at baseline , posttreatment , and 1-year follow-up . The wait list group was assessed at baseline , after a 4-month waiting period , at posttreatment , and after 1 year . The primary outcome measure was the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS The CBTp group showed significant improvement over the wait list group for the total PANSS score at posttreatment-postwaiting . CBTp was also superior to the wait list group in regard to the secondary outcomes positive symptoms , general psychopathology , depression , and functioning , but not in regard to negative symptoms . The number of dropouts during the treatment phases was low ( 11.3 % ) . Participants perceived the treatment as helpful ( 98 % ) and considered themselves improved ( 92 % ) . Significant pre- and posttreatment effect sizes varied between 0.77 for general psychopathology and 0.38 for delusional conviction . The positive effects of treatment could be maintained at 1-year follow-up , although the number of patients who had deteriorated was higher than at post assessment . CONCLUSIONS Large proportions of patients in clinical practice setting s benefit from CBTp . The efficacy of CBTp can be generalized to clinical practice despite the differences in patients , therapists , and deliverance |
455 | 26,314,706 | Irrespective of the method of capturing PROs or FPS , the quantified level of association between these two areas was moderate at best , providing evidence that FPS and PRO assessment s offer unique information to assist clinicians in their decision-making | Purpose The process of assessing patient symptoms and functionality using patient-reported outcomes ( PROs ) and functional performance status ( FPS ) is an essential aspect of patient-centered oncology research and care .
However , PRO and FPS measures are often employed separately or inconsistently combined .
Thus , the purpose of this study was to conduct a systematic review of the level of association between PRO and FPS measures to determine their differential or combined utility . | PURPOSE To determine the effects of breast cancer-specific print material s and step pedometers on physical activity ( PA ) and quality of life ( QoL ) in breast cancer survivors . PATIENTS AND METHODS Breast cancer survivors ( N = 377 ) were r and omly assigned to receive one of the following : a st and ard public health recommendation for PA , previously developed breast cancer-specific PA print material s , a step pedometer , or a combination of breast cancer-specific print material s and step pedometers . The primary outcome was self-reported moderate/vigorous PA minutes per week . Secondary outcomes were QoL ( Functional Assessment of Cancer Therapy-Breast ) , fatigue , self-reported brisk walking , and objective step counts . Assessment s were conducted at baseline and postintervention ( 12 weeks ) . RESULTS Attrition was 10.3 % ( 39 of 377 ) . On the basis of linear mixed-model analyses , PA increased by 30 minutes/week in the st and ard recommendation group compared with 70 minutes/week in the print material group ( mean difference , 39 minutes/week ; 95 % CI = -10 to 89 ; d = 0.25 ; P = .117 ) , 89 minutes/week in the pedometer group ( mean difference , 59 minutes/week ; 95 % CI , 11 to 108 ; d = 0.38 ; P = .017 ) , and 87 minutes/week in the combined group ( mean difference , 57 minutes/week ; 95 % CI , 8 to 106 ; d = 0.37 ; P = .022 ) . For brisk walking minutes/week , all three intervention groups reported significantly greater increases than the st and ard recommendation group . The combined group also reported significantly improved QoL ( mean difference , 5.8 ; 95 % CI , 2.0 to 9.6 ; d = 0.33 ; P = .003 ) and reduced fatigue ( mean difference , 2.3 ; 95 % CI , 0.0 to 4.7 ; d = 0.25 ; P = .052 ) compared with the st and ard recommendation group . CONCLUSION Breast cancer-specific PA print material s and pedometers may be effective strategies for increasing PA and QoL in breast cancer survivors . A combined approach appears to be optimal . CLINICAL TRIAL REGISTRATION Clinical Trials.gov Identifier The Sickness Impact Profile ( SIP ) and the Hospital Anxiety and Depression scale ( HAD ) were used for assessment of physical and psychosocial functioning and emotional distress in patients with small cell lung cancer ( SCLC ) receiving chemotherapy . Treatment schedules extended over 12 months . Before treatment sixty-two patients , 36 - 80 years of age , completed the question naires and a selection of lung cancer symptom items . Approximately 50 % of the patients reported clinical ly significant physical dysfunction , while emotional distress was reported by 25 % and social restraints by 40 % . Self-reported overall dysfunction , as assessed by SIP total index , was clinical ly significant in 60 % of the patients . SIP physical and total indices were strongly related to WHO performance status ( grade 0 - 4 ) . The assessment was subsequently repeated every third month during the treatment period . Overall tumour response rate was 82 % . The changes of physical and psychosocial functioning , as assessed by SIP , were significantly related to tumour response , although a persistent substantial overall dysfunction was shown among 50 % of the responders after 3 months and among c. 40 % after 6 months . In addition to tumour response , pain and appetite changes correlated with the change of overall SIP in multivariate analysis , implying the importance of pain control and appetite stimulating measures for patients with advanced cancer . Anxiety and depression , as measured by HAD , were reduced in 21 patients who completed 12 months chemotherapy , but only anxiety co-varied with tumour response . The results lend support to the use of the generic SIP and HAD as outcome measures in clinical research with SCLC patients receiving chemotherapy Breast cancer ( BC ) patients experience multiple symptoms as a result of diagnosis and treatment . While surveillance for detecting cancer recurrence is fundamental to follow-up care , managing symptoms , and promoting health behaviors are equally important . UCSF has implemented a secure online health question naire enabling BC patients to provide up date s of their health history and symptoms . We r and omly selected a sample of stage I – III BC patients ( n = 106 ) who completed a question naire before a medical oncology visit between August 2010 and January 2011 and consented to have data used for research . We conducted a chart review calculating the number of symptoms reported in the question naire , the clinic note only , and both question naire and clinic note , excluding chronic symptoms addressed previously . Self-reported data on exercise and alcohol consumption was compared to documentation of these lifestyle factors in clinic notes . Patients reported significantly more symptoms using the online question naire ( mean = 3.8 , range 0–13 ) than were documented by the provider in clinic notes ( mean = 1.8 , range 0–7 ; p < 0.001 for the difference ) . A regression plot comparing the percentage of symptoms agreed upon by the patient and provider and the percentage of symptoms addressed yields a slope of 0.56 ( 95 % CI 0.41–0.71 ) . The number of self-reported symptoms correlates with self-reported Karnofsky scale such that the number of symptoms reported by the patient increases linearly with this score until a threshold and it then plateaus ( p < 0.001 ) . Exercise behavior and alcohol consumption were reported in 100 % of the online question naires , but was documented in only 30/106 ( 28 % ) and 75/106 ( 70 % ) of charts review ed . In 19/75 ( 25 % ) charts with alcohol consumption documented , there was substantial discordance between patient and clinician reporting . Electronic data collection of BC patient-reported outcomes has a positive effect on symptom management and identification of opportunities for risk-reducing behavior change 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 OBJECTIVE The interpretation of health-related quality of life ( HRQL ) data from clinical trials can be enhanced by underst and ing the degree of change in HRQL scores that is considered meaningful . Our objectives were to combine distribution-based and two anchor-based approaches to identify minimally important differences ( MIDs ) for the 27-item Trial Outcome Index ( TOI ) , the seven-item Social Well-Being ( SWB ) subscale , and the six-item Emotional Well-being ( EWB ) subscale from the Functional Assessment of Cancer Therapy-Biological Response Modifiers ( FACT-BRM ) instrument . METHODS Distribution-based MIDs were based on the st and ard error of measurement . Anchor-based approaches utilized patient-reported global rating of change ( GRC ) and change in physician-reported performance status rating ( PSR ) . Correlations and weighted kappa statistics were used to assess association and agreement between the two anchors . FACT-BRM changes were evaluated for three time periods : baseline to month 1 , month 2 to month 3 , and month 5 to month 6 . RESULTS Association between GRC and change in PSR was poor . Correlation between the anchors and HRQL change scores was largest at month 1 and decreased through month 6 . Combining results from all approaches , the MIDs identified were 5 - 8 points for the TOI , 2 points for the SWB subscale , and 2 - 3 points for the EWB subscale . CONCLUSIONS We combined patient-reported estimates , physician-reported estimates , and distribution-based estimates to derive MIDs for HRQL outcomes from the FACT-BRM . These results will enable interpretation of treatment group effects in a clinical trial setting , and they can be used to estimate sample size or power when design ing future studies BACKGROUND Patient-reported outcomes ( PROs ) are essential for evaluating treatment effects on health-related quality of life and symptoms from the patient 's perspective . This study sought to evaluate the psychometric properties of the nine-item Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network Colorectal Cancer Symptom Index ( FCSI-9 ) in a metastatic colorectal cancer ( mCRC ) population . METHODS The FCSI-9 and EQ-5D were administered every 2 - 4 weeks to mCRC subjects in a phase III clinical trial . Three hundred ninety-one mCRC subjects completed the question naires at baseline and at least one follow-up assessment . Internal consistency reliability , test-retest reliability , construct validity , known groups validity , responsiveness , and the minimum important difference ( MID ) of the FCSI-9 were evaluated . RESULTS The internal consistency and test-retest reliability of the FCSI-9 were acceptable ( 0.81 and 0.76 , respectively ) . Construct validity was supported based on moderate correlations with the EQ-5D . Known groups validity was evaluated by examining the FCSI-9 scores of subjects categorized by their Eastern Cooperative Oncology Group performance status ( PS ) score . Subjects with better PS scores reported significantly higher FCSI-9 scores than those with lower PS scores at both baseline and week 8 . Responsiveness , as measured by Guyatt 's statistic , was 0.77 from baseline to week 8 and 0.60 from week 4 to week 12 . Considering all data together , the MID of the FCSI-9 is estimated to be in the range of 1.5 - 3.0 points . CONCLUSION Results provide preliminary evidence of the reliability , validity , and responsiveness of the FCSI-9 The st and ard approach for documenting symptomatic adverse events ( AEs ) in cancer clinical trials involves investigator reporting using the National Cancer Institute 's ( NCI 's ) Common Terminology Criteria for Adverse Events ( CTCAE ) . Because this approach underdetects symptomatic AEs , the NCI issued two contracts to create a patient-reported outcome ( PRO ) measurement system as a companion to the CTCAE , called the PRO-CTCAE . This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties . A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting . For each of these , a PRO-CTCAE plain language term in English and one to three items characterizing the frequency , severity , and /or activity interference of the AE were created , rendering a library of 124 PRO-CTCAE items . These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational , racial , and geographic background s. Favorable measurement properties of the items , including construct validity , reliability , responsiveness , and between-mode equivalence , were determined prospect ively in a demographically diverse population of patients receiving treatments for many different tumor types . A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing . Work is ongoing to translate the PRO-CTCAE into multiple language s and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses . It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research Data from a clinical study of 86 pancreatic cancer patients with involuntary , significant weight loss ( cachexia ) were used to explore the relationship between patient-reported outcomes ( PROs ) and survival . In all , 28 pancreatic cancer patients with cachexia were given gemcitabine ( Gemzar ) plus 3 mg/kg of infliximab ( Remicade ) , 28 were given gemcitabine plus 5 mg/kg of infliximab , and 30 were given gemcitabine plus placebo in a double-blinded , phase II , multicenter trial . PRO endpoints included scores from the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , Functional Assessment of Anorexia/ Cachexia Therapy ( FAACT ) , Brief Pain Inventory ( BPI ) , and the Short-Form 36 general health survey ( SF-36 ) . Population mean scores at baseline indicated fatigue problems ( FACIT-F ) , nutritional health issues ( FAACT ) , and mild-to-moderate pain ( BPI " worst pain " score ) . Baseline normalized SF-36 values for physical functioning , vitality , and mental health indicated substantial impairment . Baseline fatigue and physical-functioning scores predicted survival as well as , or better than , baseline Karnofsky Performance Status or hemoglobin level . A cut-point in the FACIT-F score ( median < or = 30 ) strongly predicted mortality ; patients with greater fatigue had a lower median overall survival than did those with less fatigue . These findings supported several features of an a priori clinical -benefit model . Patient-reported fatigue provided powerful prognostic information ; tracking of this symptom may be useful for treatment planning and medical monitoring of advanced-stage pancreatic cancer patients with cachexia . These results must be confirmed by larger trials |
456 | 25,450,495 | Primary studies infrequently reported strategies to enhance cultural relevance .
Exploratory moderator analyses found no evidence that associated cultural relevance strategies with better medication adherence outcomes . | OBJECTIVE This meta- analysis systematic ally compiles intervention research design ed to increase medication adherence among underrepresented adults . | We evaluated the efficacy of LifeWindows , a theory-based , computer-administered antiretroviral ( ARV ) therapy adherence support intervention , delivered to HIV + patients at routine clinical care visits . 594 HIV + adults receiving HIV care at five clinics were r and omized to intervention or control arms . Intervention vs. control impact in the intent-to-treat sample ( including participants whose ARVs had been entirely discontinued , who infrequently attended care , or infrequently used LifeWindows ) did not reach significance . Intervention impact in the On Protocol sample ( 328 intervention and control arm participants whose ARVs were not discontinued , who attended care and were exposed to LifeWindows regularly ) was significant . On Protocol intervention vs. control participants achieved significantly higher levels of perfect 3-day ACTG-assessed adherence over time , with sensitivity analyses maintaining this effect down to 70 % adherence . This study supports the utility of LifeWindows and illustrates that patients on ARVs who persist in care at clinical care sites can benefit from adherence promotion software . ResumenEvaluamos la eficacia de LifeWindows , una intervención de apoyo para la adherencia a la terapia antirretroviral ( TAR ) basada en teoría y con administración informatizada para pacientes con VIH + en sus visitas clínicas rutinarias . 594 adultos de cinco clínicas con VIH + y bajo tratamiento fueron aleatoriamente asignados a un grupo de intervención o de control . No se alcanzó significación estadística al comparar ambos grupos bajo la estrategia de ‘ intención de tratar ’ ( incluyendo los participantes cuyos TAR se habían interrumpido por completo , habían asistido a la clínica en pocas ocasiones , o usaron LifeWindows con poca frecuencia ) . Sin embargo , la intervención obtuvo un impacto significativo cu and o se evaluó con la muestra bajo Protocol o ( un total de 328 participantes cuyos TAR no fueron interrumpidos , asistieron a sus visitas clínicas y se expusieron a LifeWindows regularmente ) . Los participantes bajo Protocol o de intervención obtuvieron niveles más altos de adherencia que el grupo control en tres días de Estudios de Grupos Clinicos con SIDA ( EGCS ) con repetidas evaluaciones y manteniendo como mínimo un 70 % de la adherencia . Este estudio apoya la utilidad de LifeWindows e indica que los pacientes con TAR que asisten a las visitas clínicas , pueden beneficiarse de este software de promoción de la adherencia Background : There is a lack of effective behavioral interventions for HIV-positive injection drug users ( IDUs ) . We sought to evaluate the efficacy of an intervention to reduce sexual and injection transmission risk behaviors and to increase utilization of medical care and adherence to HIV medications among this population . Methods : HIV-positive IDUs ( n = 966 ) recruited in 4 US cities were r and omly assigned to a 10-session peer mentoring intervention or to an 8-session video discussion intervention ( control condition ) . Participants completed audio computer-assisted self-interviews and had their blood drawn to measure CD4 cell count and viral load at baseline and at 3-month ( no blood ) , 6-month , and 12-month follow-ups . Results : Overall retention rates for r and omized participants were 87 % , 83 % , and 85 % at 3 , 6 , and 12 months , respectively . Participants in both conditions reported significant reductions from baseline in injection and sexual transmission risk behaviors , but there were no significant differences between conditions . Participants in both conditions reported no change in medical care and adherence , and there were no significant differences between conditions . Conclusions : Both interventions led to decreases in risk behaviors but no changes in medical outcomes . The characteristics of the trial that may have contributed to these results are examined , and directions for future research are identified Purpose The purpose of this study was to examine whether integrating depression treatment into care for type 2 diabetes mellitus among older African Americans improved medication adherence , glycemic control , and depression outcomes . Methods Older African Americans prescribed pharmacotherapy for type 2 diabetes mellitus and depression from physicians at a large primary care practice in west Philadelphia were r and omly assigned to an integrated care intervention or usual care . Adherence was assessed at baseline , 2 , 4 , and 6 weeks using the Medication Event Monitoring System to assess adherence . Outcomes assessed at baseline and 12 weeks included st and ard laboratory tests to measure glycemic control and the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression . Results In all , 58 participants aged 50 to 80 years participated . The proportion of participants who had 80 % or greater adherence to an oral hypoglycemic ( intervention 62.1 % vs usual care 24.1 % ) and an antidepressant ( intervention 62.1 % vs usual care 10.3 % ) was greater in the intervention group in comparison with the usual care group at 6 weeks . Participants in the integrated care intervention had lower levels of glycosylated hemoglobin ( intervention 6.7 % vs usual care 7.9 % ) and fewer depressive symptoms ( CES-D mean scores : intervention 9.6 vs usual care 16.6 ) compared with participants in the usual care group at 12 weeks . Conclusion A pilot r and omized controlled trial integrating type 2 diabetes mellitus treatment and depression was successful in improving outcomes among older African Americans . Integrated interventions may be more feasible and effective in real-world practice s with competing dem and s for limited re sources Background Hypertension is more prevalent and clinical ly severe among African – Americans than whites . Several health behaviors influence blood pressure ( BP ) control , but effective , accessible , culturally sensitive interventions that target multiple behaviors are lacking . Purpose We evaluated a culturally adapted , automated telephone system to help hypertensive , urban African – American adults improve their adherence to their antihypertensive medication regimen and to evidence -based guidelines for dietary behavior and physical activity . Methods We r and omized 337 hypertensive primary care patients to an 8-month automated , multi-behavior intervention or to an education-only control . Medication adherence , diet , physical activity , and BP were assessed at baseline and every 4 months for 1 year . Data were analyzed using longitudinal modeling . Results The intervention was associated with improvements in a measure of overall diet quality ( + 3.5 points , p < 0.03 ) and in energy expenditure ( + 80 kcal/day , p < 0.03 ) . A decrease in systolic BP between groups was not statistically significant ( −2.3 mmHg , p = 0.25 ) . Conclusions Given their convenience , scalability , and ability to deliver tailored messages , automated telecommunications systems can promote self-management of diet and energy balance in urban African – Americans Optimists ( people who have positive expectations about the future ) have been shown to perform more health-promoting behaviors than pessimists . This study attempts to alter individuals ’ levels of optimism , and thereby their health behaviors , by having them write about a positive future . HIV-infected women ( N = 40 ) on combination therapies were r and omly assigned to write about a positive future or assigned to a no-writing control group . Among participants who were low in optimism , the writing intervention led to increased optimism , a trend toward increased self-reported adherence to medications , and decreased distress from medication side effects , compared to controls who did not write . Participants who were high in optimism showed the opposite effects after writing about the future . Results suggest that a future-oriented writing intervention may be a promising technique to increase medication adherence and decrease symptom , distress in pessimistic individuals A r and omized 2-group medication adherence intervention is evaluated with HIV-infected adults ( N = 141 ) assessed at baseline , 3- , and 9-month follow-ups . Cognitive ( self-efficacy , behavioral intent ) , mental health ( depression , well-being ) , and substance use indicators were the outcome measures . In addition , a posttest-only analysis from 3 to 9 months evaluates intervention impact on antiretroviral adherence , measured through Medication Event Monitoring System and pill counts . Compared to the st and ard care group , the intervention group showed significant increases in adherence self-efficacy and behavioral intent at 3 and 9 months and marginal improvements in mental health . Although the st and ard care group had higher adherence at 3 months ( no baseline data were available prior to intervention ) , intervention group patients showed significant increases in adherence from 3 to 9 months . Although adherence levels achieved by intervention patients may not be sufficient for virological control , this is one of the first studies to provide promising results of longer term effectiveness of a behavioral adherence intervention Background Up to 50 % of patients do not take medications as prescribed . Interventions to improve adherence are needed , with an underst and ing of which patients benefit most . Objective To test the effect of two low-literacy interventions on medication adherence . Design R and omized controlled trial , 2 × 2 factorial design . Participants Adults with coronary heart disease in an inner-city primary care clinic . Interventions For 1 year , patients received usual care , refill reminder postcards , illustrated daily medication schedules , or both interventions .Main Measures The primary outcome was cardiovascular medication refill adherence , assessed by the cumulative medication gap ( CMG ) . Patients with CMG < 0.20 were considered adherent . We assessed the effect of the interventions overall and , post-hoc , in subgroups of interest . Key Results Most of the 435 participants were elderly ( mean age = 63.7 years ) , African-American ( 91 % ) , and read below the 9th- grade level ( 78 % ) . Among the 420 subjects ( 97 % ) for whom CMG could be calculated , 138 ( 32.9 % ) had CMG < 0.20 during follow-up and were considered adherent . Overall , adherence did not differ significantly across treatments : 31.2 % in usual care , 28.3 % with mailed refill reminders , 34.2 % with illustrated medication schedules , and 36.9 % with both interventions . In post-hoc analyses , illustrated medication schedules led to significantly greater odds of adherence among patients who at baseline had more than eight medications ( OR = 2.2 ; 95 % CI , 1.21 to 4.04 ) or low self-efficacy for managing medications ( OR = 2.15 ; 95 % CI , 1.11 to 4.16 ) ; a trend was present among patients who reported non-adherence at baseline ( OR = 1.89 ; 95 % CI , 0.99 to 3.60 ) . Conclusions The interventions did not improve adherence overall . Illustrated medication schedules may improve adherence among patients with low self-efficacy , polypharmacy , or baseline non-adherence , though this requires confirmation Treatment advocacy ( TA ) programs , based in AIDS service organizations and clinics , aim to engage clients into care and support antiretroviral treatment ( ART ) adherence through client-centered counseling ; advocate for patients with providers ; and provide social service referrals . Systematic evaluations of TA are lacking . We conducted a non-r and omized evaluation examining relationships of TA participation to adherence , care engagement , social services utilization , unmet needs , patient self-advocacy , and adherence self-efficacy among 121 HIV-positive clients ( 36 in TA , 85 not in TA ; 87 % male , 34 % African American , 31 % White , 19 % Latino ) . In multivariate models , TA participants ( vs. non-TA participants ) showed higher electronically monitored [ 85.3 % vs. 70.7 % of doses taken ; b(SE ) = 13.16(5.55 ) , p < .05 ] and self-reported [ 91.1 % vs. 75.0 % ; b(SE ) = 11.60(5.65 ) , p < .05 ] adherence ; utilized more social service programs [ Ms = 5.2 vs. 3.4 ; b(SE ) = 1.97(0.48 ) , p < .0001 ] ; and had fewer unmet social-service needs [ Ms = 1.8 vs. 2.7 ; b(SE ) = -1.06(0.48 ) , p < .05 ] . Findings suggest the need for a r and omized controlled trial of TA BACKGROUND To improve medication adherence in cardiac patients , in partnership with a safety-net provider , this research team developed and evaluated a low-literacy medication education tool . METHODS Using principles of community-based participatory research , the team developed a prototype of a low-literacy hospital discharge medication education tool , customizable for each patient , featuring instruction-specific icons and pictures of pills . In 2007 , a r and omized controlled clinical trial was performed , testing the tool 's effect on posthospitalization self-reported medication adherence and knowledge , 2 weeks postdischarge in English- and Spanish-speaking safety-net in patients . To vali date the self-report measure , 4 weeks postdischarge , investigators collected self-reports of the number of pills remaining for each medication in a sub sample of participants . Nurses rated tool acceptability . RESULTS Among the 166/210 eligible participants ( 79 % ) completing the Week-2 interview , self-reported medication adherence was 70 % ( 95 % CI=62 % , 79 % ) in intervention participants and 78 % ( 95 % CI=72 % , 84 % ) in controls ( p=0.13 ) . Among the 85 participants ( 31 % ) completing the Week-4 interview , self-reported pill counts indicated high adherence ( greater than 90 % ) and did not differ between study arms . Self-reported adherence was correlated with self-reported pill count in intervention participants ( R=0.5 , p=0.004 ) but not in controls ( R=0.07 , p=0.65 ) . There were no differences by study arm in medication knowledge . The nurses rated the tool as highly acceptable . CONCLUSIONS Although the evaluation did not demonstrate the tool to have any effect on self-reported medication adherence , patients who received the schedule self-reported their medication adherence more accurately , perhaps indicating improved underst and ing of their medication regimen and awareness of non-adherence The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy , patient-provider relationships , and adherence to HAART was examined . Evaluations were conducted at baseline , 6 weeks , and 6 months for participants ( n = 85 ) r and omly assigned to either the intervention group or a comparison group ; 69 ( 81 % ) remained in the study for the entire 6-month duration . The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures , at 6 months . While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management , baseline to 6 weeks , no other changes were significant . Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks ( p = 0.04 ) and at 6 months ( p < 0.001 ) . The comparison group showed little change baseline to 6 weeks and baseline to 6 months . While there was a trend for the pilot group to report better medication adherence , these differences were not statistically significant . Further evaluation of the impact of this adherence enhancement program is needed OBJECTIVE To determine the efficacy of an automated , interactive , telephone-based health communication intervention for improving glaucoma treatment adherence among patients in 2 hospital-based eye clinics . METHOD A total of 312 patients with glaucoma ( 18 - 80 years of age ) were enrolled in a r and omized controlled trial at 2 eye clinics located in hospitals in the southeastern United States . These patients were considered nonadherent because they did not take their medication , refill their medication , and /or keep their appointments . The treatment group received an automated , interactive , tailored , telephone-based health communication intervention and tailored print material s. The control group received usual care . MAIN OUTCOME MEASURES Adherence with medication taking , prescription refills , and appointment keeping measured by interviews , medical charts , appointment records , and pharmacy data . RESULTS A statistically significant increase was found for all adherence measures in both the intervention and control groups . Interactive telephone calls and tailored print material s did not significantly improve adherence measures compared with controls . CONCLUSIONS During the study period , patient adherence to glaucoma treatment and appointment keeping improved in both study arms . Participation in the study and interviews may have contributed . Strategies that address individuals ' barriers and facilitators may increase the impact of telephone calls , especially for appointment keeping and prescription refills . APPLICATION TO CLINICAL PRACTICE Glaucoma patient care should include reminders about consistent use of medication and the importance of keeping appointments . More frequent , and personalized , telephone contact may be helpful to patients who are known to be nonadherent . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00794170 Child sexual abuse ( CSA ) is associated with HIV risk behaviors [ Bensley , L. , Van Eenwyk , J. , and Simmons , K. W. , 2003 . ] and more prevalent among women living with HIV than in the general population [ Koenig , L. J. , and Clark , H. , 2004 ] . This r and omized Phase ~ I clinical trial tested the impact of a culturally congruent psychoeducational intervention design ed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories . An ethnically diverse sample of 147 women were r and omized to two conditions : an 11-session Enhanced Sexual Health Intervention ( ESHI ) or an attention control . Results based on “ intent to treat ’ ’ analysesof pre – post changes are reported here . Additional analyses explored whether theobserved effects might depend on “ intervention dose , ’ ’ i.e. , number of sessions attended . Women in the ESHI condition reported greater sexual risk reduction than women in the control condition . Although there were no differences between women in the ESHI and control groups on medication adherence , women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women . The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA , and highlight the importance of addressing the effects of CSA on sexual risk reduction and medicationadherence in preventive interventions for women Affordable and effective antiretroviral therapy ( ART ) adherence interventions are needed for many patients to promote positive treatment outcomes and prevent viral resistance . We conducted a two-arm r and omized trial ( n = 40 men and women receiving and less than 95 % adherent to ART ) to test a single office session followed by four biweekly cell phone counseling sessions that were grounded in behavioral self-management model of medication adherence using data from phone-based unannounced pill counts to provide feedback-guided adherence strategies . The control condition received usual care and matched office and cell phone/pill count contacts . Participants were baseline assessed and followed with biweekly unannounced pill counts and 4-month from baseline computerized interviews ( 39/40 retained ) . Results showed that the self-regulation counseling delivered by cell phone demonstrated significant improvements in adherence compared to the control condition ; adherence improved from 87 % of pills taken at baseline to 94 % adherence 4 months after baseline , p < 0.01 . The observed effect sizes ranged from moderate ( d = 0.45 ) to large ( d = 0.80 ) . Gains in adherence were paralleled with increased self-efficacy ( p < 0.05 ) and use of behavioral strategies for ART adherence ( p < 0.05 ) . We conclude that the outcomes from this test of concept trial warrant further research on cell phone-delivered self-regulation counseling in a larger and more rigorous trial The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P < .01 ) , lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P < .01 ) , and lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P < .01 ) compared with participants in the usual care group at 6 weeks . Compared with the usual care group , the proportion of participants in the intervention group who had 80 % or greater adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P < .01 ) and to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P < .001 ) was greater at 6 weeks . CONCLUSION A pilot , r and omized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources Background . Patients cite " forgetting " as a reason for nonadherence to highly active antiretroviral therapy ( HAART ) . We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects . Methods . The study was a prospect i ve , r and omized , controlled trial involving 64 HIV-infected adults . The intervention was the Disease Management Assistance System ( DMAS ) device , combined with monthly adherence counseling . Control subjects received only adherence counseling . The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times . Adherence was measured for 24 weeks using electronic drug exposure monitor ( eDEM ) caps . Results . A total of 58 subjects completed the 24-week study period ; 28 were HAART naive ( 12 DMAS users and 16 control subjects ) . Mean adherence scores did not differ significantly between DMAS users ( 80 % ) and control subjects ( 65 % ) . Post hoc analysis of 31 memory-impaired subjects ( 14 DMAS users and 17 control subjects ) revealed significantly higher adherence rates among DMAS users ( 77 % ) , compared with control subjects ( 57 % ) ( P=.001 ) . However , analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users ( 83 % ) , compared with control subjects ( 77 % ) ( P=.25 ) . At week twelve , 38 % of the DMAS users and 14 % of the control subjects had an undetectable plasma HIV RNA load ( P=.014 ) , and at week 24 , the plasma HIV RNA load was undetectable for 34 % of the DMAS users and 38 % of the control subjects ( P=.49 ) . CD4(+ ) cell counts did not differ between the study arms . Virological and immunological responses were not related to DMAS use in memory-impaired subjects . Conclusion . The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects This report describes a pilot study of a nursing intervention to increase adherence to combination therapy . The intervention was based on motivational interviewing ( MI ) . Participants completed a baseline assessment using the computer-administered self-interview with audio ( ACASI ) data collection method and then were r and omly assigned to the MI intervention or control condition . Nurse counselors met with participants in the MI intervention group for three adherence sessions . Two months following baseline , participants completed a follow-up assessment . Mean scores on ratings of missed medications were lower for participants in the intervention group than those in the control group . Although there were no significant differences in the number of medications missed during the past 4 days , participants in the MI group reported being more likely to follow the medication regimen as prescribed by their health care provider . The pilot study provided useful information about the acceptability of ACASI and the adequacy of intervention procedures . The results of this pilot study show promise for the use of MI as an intervention to promote adherence to antiretroviral medications Objective : To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems . Design : A r and omized controlled trial ( SMART Couples Study ) conducted between August 2000 and January 2004 . Setting : Two HIV/AIDS outpatient clinics in New York City . Participants : Heterosexual and homosexual HIV-serodiscordant couples ( n = 215 ) in which the HIV-seropositive partner had < 80 % adherence at baseline . The sample was predominantly lower-income racial/ethnic minorities . Intervention : Participants were r and omly assigned to a four-session couple-focused adherence intervention or usual care . The intervention consisted of education about treatment and adherence , identifying adherence barriers , developing communication and problem-solving strategies , optimizing partner support , and building confidence for optimal adherence . Outcome measures : Medication adherence at week 8 ( 2 weeks after the intervention ) compared with baseline , assessed with a Medication Event Monitoring System cap . Results : Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken ( 76 % versus 60 % ) or doses taken within specified time parameters ( 58 % versus 35 % ) . Also , participants in the intervention arm were significantly more likely to achieve high levels of adherence ( > 80 % , > 90 % , or > 95 % ) when compared with controls . However , in most cases , effects diminished with time , as seen at follow-up at 3 and 6 months . Conclusion : The SMART Couples program significantly improved medication adherence over usual care , although the level of improved adherence , for many participants , was still suboptimal and the effect was attenuated over time Background : We assessed the efficacy , compliance , and tolerability of the twice‐a‐day triple therapy , amoxycillin , omeprazole , and clarithromycin , for Helicobacter pylori and studied the effect of treatment duration ( 7 , 10 or 14 days ) on these factors BACKGROUND A r and omized , controlled trial was conducted to evaluate the impact of a directly administered antiretroviral therapy program ( DAART ) and intensive adherence case management ( IACM ) intervention on virologic and immunologic response to highly active antiretroviral therapy ( HAART ) among patients at 3 public human immunodeficiency virus clinics in Los Angeles County , California . METHODS Participants included 250 treatment-naive and treatment-experienced persons for whom no more than 1 prior HAART regimen had failed . Five days per week for 6 months , a community worker delivered 1 HAART dose to DAART participants and observed the participant take it . IACM participants met weekly with a case manager to overcome barriers to HAART adherence . A control group ( the st and ard of care [ SOC ] group ) received the usual care . RESULTS The majority of patients were Latino ( 64 % ) or African American ( 24 % ) ; 57 % were monolingual Spanish speakers . Seventy-five percent of the patients were male , and 64 % reported an annual income of < 10,000 dollars . In an intent-to-treat analysis , no statistical differences were observed in the percentage of patients with an undetectable viral load ( i.e. , < 400 copies/mL ) at 6 months between the DAART group ( 54 % ) , IACM group ( 60 % ) , and SOC group ( 54 % ; P>.05 ) . An on-treatment analysis determined that there were no statistical differences in the percentage of patients with an undetectable viral load at 6 months between the DAART group ( 71 % ) , IACM group ( 80 % ) , and SOC group ( 74 % ; P>.05 ) . Additionally , there were no statistical differences in 6-month changes in the CD4 + cell count or in self-reported adherence to therapy . CONCLUSIONS Among patients with limited prior HAART experience and adherence barriers that had not been assessed before r and omization , no differences were found in virologic or immunologic response for DAART or IACM , compared with SOC , at 6 months . DAART and IACM did not improve short-term outcomes when SOC included other means of adherence support that were not controlled for by the study design Purpose . Examine the effectiveness of a community-based , multimedia intervention on medication adherence among hypertensive adults . Design . R and omized controlled trial . Setting . Rural south Alabama . Subjects . Low-income adults ( N = 434 ) receiving medication at no charge from a public health department or a Federally Qualified Health Center . Intervention . Both interventions were home-based and delivered via computer by a community health advisor . The adherence promotion ( AP ) intervention focused on theoretical variables related to adherence ( e.g. , barriers , decisional balance , and role models ) . The cancer control condition received general cancer information . Measures . Adherence was assessed by pill count . Other adherence-related variables , including barriers , self-efficacy , depression , and sociodemographic variables , were collected via a telephone survey . Analysis . Chi-square analysis tested the hypothesis that a greater proportion of participants in the AP intervention are ≥80 % adherent compared to the control group . General linear modeling examined adherence as a continuous variable . Results . Participants receiving the intervention did not differ from individuals in the control group ( 51 % vs. 49 % adherent , respectively ; p = .67 ) . Clinic type predicted adherence ( p < .0001 ) , as did forgetting to take medications ( p = .01 ) and difficulty getting to the clinic to obtain medications ( p < .001 ) . Conclusions . Multilevel interventions that focus on individual behavior and community-level targets ( e.g. , how health care is accessed and delivered ) may be needed to improve medication adherence among low-income rural residents OBJECTIVE Compare the efficacy of a multicomponent social support intervention to st and ard-of-care counseling on medication adherence among HIV-infected patients initiating antiretroviral therapy . DESIGN R and omized controlled trial . Generalized estimating equations tested for differences in the percentage of participants achieving 90 % adherence . MAIN OUTCOME MEASURES Pill-taking , electronically monitored over 6 consecutive months ; plasma viral load ( VL ) , assessed at 3 and 6 months following initiation of therapy . RESULTS Of 226 participants who were r and omized and began the trial , 87 ( 38 % ) were lost to the study by 6 months . The proportion of adherent participants declined steadily over time , with no time by group interaction . Sustained adherence was associated with increased odds of achieving an undetectable VL ( OR=1.78 ; 95 % CI=1.01 , 3.13 ) . In intention-to-treat analyses , a larger proportion of the intervention group than the control group was adherent ( 40.15 % vs. 27.59 % , p=.02 ) and achieved an undetectable VL p=.04 ) . However , the majority of participants who remained on study experienced some reduction in VL ( > or=1-log drop or undetectable ) , regardless of experimental condition . CONCLUSION The multicomponent social support intervention significantly improved medication adherence over st and ard-of-care counseling ; evidence for improved virologic outcomes was inconsistent . Early discontinuation of care and treatment may be a greater threat to the health of HIV patients than imperfect medication-taking The problem of medication adherence is pronounced in hypertensive black men . However , factors influencing their adherence are not well understood . This secondary analysis of the ongoing Counseling African Americans to Control Hypertension ( CAATCH ) r and omized clinical trial investigated the patient , provider , and health care system factors associated with medication adherence among hypertensive black men . Participants ( N=253 ) were aged 56.6±11.6 years , earned < $ 20,000 yearly ( 72.7 % ) , and almost one half were on Medicaid ( 44 % ) . Mean systolic blood pressure was 148.7±15.8 mm Hg and mean diastolic blood pressure was 92.7±9.8 mm Hg . Over one half of participants ( 54.9 % ) were nonadherent . In a hierarchical regression analysis , the patient factors that predicted medication adherence were age , self-efficacy , and depression . The final model accounted for 32.1 % of the variance ( F=7.80 , df 10 , 165 , P<.001 ) . In conclusion , age , self-efficacy , and depression were associated with antihypertensive medication adherence in black men followed in Community/Migrant Health Centers . Age is a characteristic that may allow clinicians to predict who may be at risk for poor medication adherence . Depression can be screened for and treated . Self-efficacy is modifiable and its implication s for practice would be the development of interventions to increase self-efficacy in black men with hypertension PURPOSE To determine the effect of several interventions on adherence to tuberculosis preventive therapy . METHODS We conducted a r and omized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis . Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly ( Supervised group , n = 99 ) , daily self-administered isoniazid with peer counseling and education ( Peer group , n = 101 ) , or routine care ( Routine group , n = 100 ) . Patients within each arm were also r and omly assigned to receive an immediate or deferred monthly $ 10 stipend for maintaining adherence . The endpoints of the trial were completing 6 months of treatment , pill-taking as measured by self-report or observation , isoniazid metabolites present in urine , and bottle opening as determined by electronic monitors in a subset of patients . RESULTS Completion of therapy was 80 % for patients in the Supervised group , 78 % in the Peer group , and 79 % in the Routine group ( P = 0.70 ) . Completion was 83 % ( 125 of 150 ) among patients receiving immediate incentives versus 75 % ( 112 of 150 ) among patients with deferred incentives ( P = 0.09 ) . The proportion of patients who were observed or reported taking at least 80 % of their doses was 82 % for the Supervised arm of the study , compared with 71 % for the Peer arm and 90 % for the Routine arm . The proportion of patients who took 100 % of doses was 77 % for the Supervised arm ( by observation ) , 6 % for the Peer arm ( by report ) , and 10 % for the Routine arm ( by report ; P < 0.001 ) . Direct observation showed the median proportion of doses taken by the Supervised group was 100 % , while electronic monitoring in a subset of patients showed the Peer group ( n = 27 ) took 57 % of prescribed doses and the Routine group ( n = 32 ) took 49 % ( P < 0.001 ) . Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold st and ard . There were no significant differences in electronically monitored adherence by type of incentive . CONCLUSION Adherence to isoniazid preventive therapy by injection drug users is best with supervised care . Peer counseling improves adherence over routine care , as measured by electronic monitoring of pill caps , and patients receiving peer counseling more accurately reported their adherence . More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups OBJECTIVE To test an educational intervention targeted to health literacy level with the goal of improving glaucoma medication adherence . METHODS One hundred and twenty-seven veterans with glaucoma were r and omized to glaucoma education or st and ard care . The intervention included a video scripted at a 4th , 7th , or 10th grade level , depending on the subject 's literacy level . After six months , the number of days without glaucoma medicine ( DWM ) according to pharmacy records for the intervention and control groups was compared . RESULTS The number of DWM in the six months following enrollment was similar for control and intervention groups ( intervention , n=67 , DWM=63 ± 198 ; st and ard care , n=60 , DWM=65 ± 198 ; p=0.708 ) . For each subgroup of literacy ( adequate , marginal , inadequate ) , subjects in the intervention group experienced less mean DWM than subjects in the control group and the effect size ( ES ) increased as literacy decreased : adequate literacy , ES 0.069 ; marginal , ES 0.183 , inadequate , ES 0.363 . Decreasing health literacy skills were associated with decreasing self-reported satisfaction with care ( slope=0.017 , SE=0.005 , p=0.002 ) . CONCLUSIONS Patients with decreased health literacy skills may benefit from educational efforts tailored to address their health literacy level and learning style . PRACTICE IMPLICATION S Providers should consider health literacy skills when engaging in glaucoma education PURPOSE Previous studies found that African American and Hispanic cancer patients are at risk for undertreatment of pain . We evaluated the efficacy of a pain education intervention for underserved minority patients . PATIENTS AND METHODS Ninety-seven underserved African American and Hispanic out patients with cancer-related pain were enrolled onto a r and omized clinical trial of pain management education . The patients in the education group received a culture-specific video and booklet on pain management . The control group received a video and booklet on nutrition . A research nurse met with each patient to review the material s. We measured changes in pain intensity and pain-related interference 2 to 10 weeks after the intervention , as well as changes in quality of life , perceived pain control , functional status , analgesics , and physician pain assessment s. RESULTS Physicians underestimated baseline pain intensity and provided inadequate analgesics for more than 50 % of the sample . Although the ratings for pain intensity and pain interference decreased over time for both groups , there was no statistically significant difference between groups . Pain education did not affect quality of life , perceived pain control , or functional status . African American patients in the education but not the control group reported a significant decrease in pain worst ratings from baseline to first follow-up ( P < .01 ) , although this decrease was not maintained at subsequent assessment s. CONCLUSION Brief education had limited impact on pain outcomes for underserved minority patients , suggesting that more intensive education for patients and interventions for physicians are needed After baseline in home interviews , 439 patients with osteoarthritis ( OA ) were r and omly assigned to the control or one of 3 intervention groups which differed only in method of delivery ( i.e. , phone , clinic , both ) . Trained non clinical interviewers review ed medications , problems with joint pain , gastrointestinal symptoms , early warning signs for common chronic diseases , scheduled outpatient visits , an evening/weekend clinic telephone number , barriers to care , and suggestions to encourage participation during clinic visits . We hypothesized that the intervention would enhance social support , satisfaction with care , morale , and medication compliance . We found that none of the interventions had any effect upon these outcomes OBJECTIVE To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with st and ard clinical care to enhance antiretroviral medication adherence . DESIGN R and omized controlled trial with follow-up . Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx , New York . The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal , spiritual , emotional , and informational adherence-related social support . MAIN OUTCOME MEASURES Medical chart- abstract ed HIV-1 RNA viral load , antiretroviral adherence according to electronic drug monitoring and participant self-report , and social support and depressive symptomatology . All assessment s conducted at baseline , 3 months , and 6 months . RESULTS Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up . Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence , higher social support , and lower depressive symptomatology at follow-up , even after controlling for baseline adherence . CONCLUSION Null findings , consistent with the limited literature on efficacious highly active antiretroviral therapy ( HAART ) adherence interventions , may be due to insufficient exposure to the intervention , its low intensity , or the nature of the sample -a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors . Overall , findings highlight the need for more comprehensive and intensive efforts to battle nonadherence Abstract Objective . To test the impact of participation in a peer-based intervention for symptom management for women living with HIV infection on selected outcome measures including , symptom intensity , medication adherence , viral control , and quality of life . Design . R and omized clinical trial . Methods . Participants were recruited using a convenient , consecutive sampling method . Those participants r and omized to the experimental condition attended seven , peer-led sessions over seven weeks . Participants r and omized to the control condition received a copy of HIV Symptom Management Strategies : A Manual for People Living with HIV/AIDS . Participants completed four surveys assessing change over time in the aforementioned outcome variables . Results . Eighty-nine HIV-infected women followed over 14 weeks and there were no differences between the two groups on baseline demographic variables . Mixed-effects regression indicated no significant difference between groups across time in total symptom intensity score and medication adherence . There was a significant difference between groups across time for two of the nine quality of life scales – HIV Mastery ( χ 2=25.08 ; p<0.005 ) and Disclosure Worries ( χ 2=24.67 ; p<0.005 ) . Conclusions . In urban-dwelling women living with HIV/AIDS , results suggest that a peer-based symptom management intervention may not decrease symptom intensity or increase medication adherence . There is positive evidence that suggests that the intervention may increase some important aspects of quality of life . However , further research is warranted to eluci date the effect of peer-based interventions in achieving positive self-management outcomes Background : The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions , but the evidence base for effective adherence interventions in human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) requires more rigorous research and reporting . Objectives : The aims of this study were to determine whether a tailored , nurse-delivered adherence intervention program-Client Adherence Profiling and Intervention Tailoring (CAP-IT)-improved adherence to HIV medications , compared with st and ard care , and to identify the relationship among adherence measures . Methods : A r and omized controlled trial ( RCT ) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period . A convenience sample of 240 participants was recruited from a freest and ing public HIV/AIDS clinic in Houston , TX , that provides medical , psychological , and pharmaceutical services for over 5,000 clients . Study instruments and measures included demographics ; chart audit to capture CD4 count , viral load , and prescribed medications ; health literacy ; and five measures of adherence ( AIDS Clinical Trial Group-Revised Reasons for Missing Medications , Morisky Self-Report of Medication Non-Adherence , Pill Count , Medication Event Monitoring System [ MEMS ] caps , and Pharmacy Refill ) . Results : A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups . Little correlation was documented among the five different adherence measures , and there was minimal correlation with clinical markers . Discussion : It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence . The findings suggest that these measures of medication adherence did not perform as expected and that , perhaps , they are not adequate measures of adherence . Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS Objective : To assess the efficacy of a behavioral intervention design ed to improve HIV medication adherence and reduce alcohol consumption among HIV-positive men and women . Design : A r and omized controlled trial conducted between July 2002 and August 2005 . Setting : A behavioral research center in New York City . Participants : HIV-positive men and women ( n = 143 ) who were on HIV antiretroviral medication and met criteria for hazardous drinking . Intervention : Participants were r and omly assigned to an 8-session intervention based on motivational interviewing and cognitive-behavioral skills building or a time- and content-equivalent educational condition . Outcome Measures : Viral load , CD4 cell count , and self-reported adherence and drinking behavior were assessed at baseline and at 3- and 6-month follow-ups . Results : Relative to the education condition , participants in the intervention demonstrated significant decreases in viral load and increases in CD4 cell count at the 3-month follow-up and significantly greater improvement in percent dose adherence and percent day adherence . There were no significant intervention effects for alcohol use , however , and effects on viral load , CD4 cell count , and adherence were not sustained at 6 months . Conclusions : An 8-session behavioral intervention can result in improvement in self-report and biologic markers of treatment adherence and disease progression . This type of intervention should be considered for dissemination and integration into HIV clinics providing comprehensive care for HIV-positive persons with alcohol problems . Although the effect was attenuated over time , future studies might test the added effectiveness of booster sessions or ongoing adherence counseling Abstract The primary aim of this study was to test an intervention to support antiretroviral medication adherence among primarily low-income men and women with HIV . The study was a r and omized controlled trial ( Get Busy Living ) with participants assigned to treatment ( Motivational Interviewing [ MI ] ) and control groups . Participants were recruited from an HIV/AIDS clinic in Atlanta , Georgia , US . Of those referred to the study , 247 completed a baseline assessment and were enrolled with 125 r and omized to the intervention group and 122 to the control group . Participants were patients beginning antiretroviral therapy or changing to a new drug regimen . The intervention consisted of five MI sessions delivered by registered nurses in individual counselling sessions . Participants were paid for each session attended . The intervention sought to build confidence , reduce ambivalence and increase motivation for ART medication-taking . Medication adherence was measured by the Medication Event Monitoring System ( MEMS ® ) from the time of screening until the final follow-up conducted approximately 12 months following the baseline assessment . Participants in the intervention condition showed a trend towards having a higher mean percent of prescribed doses taken and a greater percent of doses taken on schedule when compared to the control group during the months following the intervention period . This effect was noted beginning at about the eighth month of the study period and was maintained until the final study month . Although the finding was weaker for overall percent of prescribed doses taken , the results for the percent of doses taken on schedule suggests that the MI intervention may be a useful approach for addressing specific aspects of medication adherence , such as adherrence to a specified dosing schedule Research was conducted to apply Orem 's theoretical constructs of self-care to the problem of self-medication behaviors among black , elderly , hypertensive patients . Orem 's propositions laid the foundation for this study evaluating the effectiveness of a self-care medication program on knowledge of medication , health locus of control , and self-care medication behaviors . Data supported the conclusion that the experimental program initially improved knowledge of medication , perceived control over health , and self-care behaviors . Follow-up analysis revealed a diminutive effect on these variables . Explanations for these conclusions were then applied to Orem 's theoretical constructs of self-care OBJECTIVE To determine whether pharmaceutical care provided by a pharmacist-managed hypertension clinic results in better treatment outcomes when compared with traditional health care from a primary care physician . DESIGN Prospect i ve , controlled study SETTING Veterans Affairs Medical Center , Philadelphia , Pennsylvania . PATIENTS Fifty six patients with essential hypertension ; 27 were r and omly assigned to the intervention group and 29 to the control group . INTERVENTION Patients in the intervention group were scheduled monthly to meet with a clinical pharmacist who made appropriate changes in prescribed drugs , adjusted dosages , and provided drug counseling in accordance with the hypertension guidelines in the sixth report of the Joint National Committee on the Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) . Patients in the control group received st and ard care from their physicians . The study period was 6 months . MEASUREMENTS AND MAIN RESULTS Treatment outcomes were measured by changes in compliance , blood pressure , and patient satisfaction . The Short Form-36 health survey and a patient satisfaction survey were used to measure changes in patient satisfaction , and a compliance evaluation survey measured compliance . Twenty-one ( 81 % ) patients in the intervention group attained their blood pressure goal of below 140/90 mm Hg at the completion of the study versus only eight ( 30 % ) in the control group ( p < 0.0001 ) . Of 11 patients with diabetes in the intervention group , 10 ( 91 % ) attained their blood pressure goal ( < 130/80 mm Hg ) versus only two ( 12 % ) of 16 patients with diabetes in the control group ( p < 0.0001 ) . No significant differences in patient satisfaction or compliance were reported between the intervention and control groups . CONCLUSIONS Pharmaceutical care improves blood pressure control and results in more patients with hypertension reaching their blood pressure goal |
457 | 27,422,595 | SFA for RCSP confers benefit over generalised approaches up to six weeks but this benefit is not apparent by 3 months .
Early changes in pain are not clinical ly significant . | BACKGROUND Rotator cuff related shoulder pain ( RCSP ) is common with a range of conservative treatments currently offered .
Evidence supporting superiority of one approach over another is lacking .
Scapula focused approaches ( SFA ) are frequently prescribed and warrant investigation .
OBJECTIVE To evaluate the effectiveness of SFA in RCSP . | BACKGROUND While physical therapy is an effective element in the rehabilitation of rotator cuff ( RC ) disease , the most effective sequence of exercise training interventions has not been defined . HYPOTHESIS/ PURPOSE The purpose of this study is to determine if there is a difference in pain or function in patients who are given RC strengthening prior to or after initiating scapular stabilization exercises . STUDY DESIGN Level I r and omized crossover trial . METHODS This was a prospect i ve study of 26 men and 14 women with a mean age 51 who were diagnosed with subacromial impingement syndrome ( SAIS ) . They were r and omly assigned to one of two groups for a comprehensive and st and ardized rehabilitation program over six visits at an orthopedic outpatient clinic . One group was prescribed a 4-week program of scapular stabilization exercises while the other group began with RC strengthening exercises . The crossover design had each group add the previously excluded four exercises to their second month of rehabilitation . RESULTS The results showed significant improvements in pain ( p < 0.001 ) , function ( p < 0.001 ) , and patient satisfaction ( p < 0.001 ) at all follow-up times for both groups . There was not a statistically significant difference in pain or function at any follow-up period for initiating one group of exercise before the other ( p > 0.05 ) . There was a statistically significant interaction between the patient 's global rating of change at the 4 week follow-up as compared to 8 weeks ( p = 0.04 ) or 16 ( p < 0.001 ) . CONCLUSION Patients with SAIS demonstrate improvement in pain and function with a st and ardized program of physical therapy regardless of group exercise sequencing . LEVEL OF EVIDENCE 1b Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up . The purpose s of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score , rotator cuff status and radiological findings influenced the outcome . Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been r and omised to a specific exercise programme or unspecific exercises ( controls ) . After 3 months of exercises , the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up . 1 year after inclusion or 1 year after surgery , the number of patients who decided to have surgery in each group was compared . The choice of surgery was related to the baseline Constant-Murley score , ultrasound and radiographs taken at inclusion . Results All patients had improved significantly ( p<0.0001 ) in the Constant-Murley score at the 1-year follow-up . Significantly more patients in the control group decided to have surgery ( 63 % ) than those in the specific exercise group ( 24 % ; p<0.0001 ) . Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear . Patients with partial tears did not differ from those with intact tendons . Interpretation The positive short-term results of specific exercises were maintained after 1 year , and this exercise strategy reduces the need for surgery . Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome . Trial registration number Clinical trials NCT01037673 Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Aim : To test the hypothesis that work related mechanical and psychosocial factors predict new onset shoulder pain in newly employed workers . Methods : Two year prospect i ve study of newly employed workers from 12 diverse occupational setting s. At baseline , 1081 subjects provided information on work related mechanical and psychosocial risk factors , and current pain status . Results : In all , 803 ( 74 % ) subjects were free from shoulder pain at baseline . Of those , 638 ( 79 % ) responded at 12 months and 476 ( 88 % ) at 24 months . New onset shoulder pain was reported by 93 ( 15 % ) and 73 ( 15 % ) subjects respectively . An increased risk of symptom onset was found in subjects reporting mechanical exposures involving heavy weights including lifting with one or two h and s , carrying on one shoulder , lifting at or above shoulder level , and pushing or pulling . Working with h and s above shoulder level was also predictive of new onset shoulder pain . Of the psychosocial factors examined , the strongest predictor was monotonous work . Those individuals with any other previous pain also had an increased risk of new onset shoulder pain at follow up . In multivariate analysis , lifting heavy weights with one or two h and s , pushing or pulling heavy weights , working with h and s above shoulder level , and monotonous work were independently associated with new onset shoulder pain . Conclusions : This study supports the hypothesised relation between mechanical risk factors and shoulder pain . In general , work related psychosocial factors were modestly associated with new onset shoulder pain . However , monotonous work was a strong risk factor for new onset shoulder pain Background : Dysfunction in the kinetic chain caused by poor scapula stabilization can contribute to shoulder injuries and Shoulder Impingement Syndrome ( SIS ) . The purpose of this study was to compare the effectiveness of two treatment approaches scapular stabilization based exercise therapy and physical therapy in patients with SIS . Methods : The study is a r and omized clinical trial in which 68 patients with SIS were r and omly assigned in two groups of exercise therapy ( ET ) and physical therapy ( PT ) and received 18 sessions of treatment . Pain , shoulders ' range of abduction and external rotation , shoulder protraction , scapular rotation and symmetry as well as postural assessment and Pectoralis minor length were evaluated pre and post intervention . The paired- sample t test and the independent sample t test were applied respectively to determine the differences in each group and between two groups . Results : Our findings indicated significant differences in abduction and external rotation range , improvement of forward shoulder translation and increase in the flexibility of the involved shoulder between the two groups ( respectively ; p=0.024 , p=0.001 , p<0/0001 , p<0/0001 ) . No significant difference was detected in pain reduction between the groups ( p=0.576 ) . Protraction of the shoulder ( p<0.0001 ) , forward head posture ( p<0/0001 ) and mid thoracic curvature ( p<0.0001 ) revealed a significant improvement in the ET group . Apparent changes occurred in scapular rotation and symmetry in both groups but no significant differences were observed between the two groups ( respectively ; p=0.183 , p=0.578 ) . Conclusion : The scapular stabilization based exercise intervention was successful in increasing shoulder range , decreasing forward head and shoulder postures and Pectoralis minor flexibility The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome . Therefore , a r and omized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome . The primary outcome measures included self-reported shoulder disability and pain . Next , patients were evaluated regarding scapular positioning and shoulder muscle strength . The scapular-focused treatment included stretching and scapular motor control training . The control therapy included stretching , muscle friction , and eccentric rotator cuff training . Main outcome measures were the shoulder disability question naire , diagnostic tests for shoulder impingement syndrome , clinical tests for scapular positioning , shoulder pain ( visual analog scale ; VAS ) , and muscle strength . A large clinical ly important treatment effect in favor of scapular motor control training was found in self-reported disability ( Cohen ’s d = 0.93 , p = 0.025 ) , and a moderate to large clinical ly important improvement in pain during the Neer test , Hawkins test , and empty can test ( Cohen ’s d 0.76 , 1.04 , and 0.92 , respectively ) . In addition , the experimental group demonstrated a moderate ( Cohen ’s d = 0.67 ) improvement in self-experienced pain at rest ( VAS ) , whereas the control group did not change . The effects were maintained at three months follow-up A systematic review of the literature was performed to evaluate the role of exercise in treating rotator cuff impingement and to synthesize a st and ard evidence -based rehabilitation protocol . Eleven r and omized , controlled trials ( level 1 and 2 ) evaluating the effect of exercise in the treatment of impingement were identified . Data regarding demographics , methodology , and outcomes of pain , range of motion , strength , and function were recorded . Individual components of each rehabilitation program were catalogued . Effectiveness was determined by statistical and clinical significance . Although many articles had method ologic concerns , the data demonstrate that exercise has statistically and clinical ly significant effects on pain reduction and improving function , but not on range of motion or strength . Manual therapy augments the effects of exercise , yet supervised exercise was not different than home exercise programs . Information regarding specific components of the exercise programs was synthesized into a gold st and ard rehabilitation protocol for future studies on the nonoperative treatment of rotator cuff impingement Background Subacromial impingement syndrome ( SIS ) is the most frequently recorded shoulder disorder . When conservative treatment of SIS fails , a subacromial decompression is warranted . However , the best moment of referral for surgery is not well defined . Both early and late referrals have disadvantages – unnecessary operations and smaller improvements in shoulder function , respectively . This paper describes the design of a new interdisciplinary treatment strategy for SIS ( TRANSIT ) , which comprises rules to treat SIS in primary care and a well-defined moment of referral for surgery . Methods / Design The effectiveness of an arthroscopic subacromial decompression versus usual medical care will be evaluated in a r and omized controlled trial ( RCT ) . Patients are eligible for inclusion when experiencing a recurrence of SIS within one year after a first episode of SIS which was successfully treated with a subacromial corticosteroid injection . After inclusion they will receive injection treatment again by their general practitioner . When , after this treatment , there is a second recurrence within a year post-injection , the participants will be r and omized to either an arthroscopic subacromial decompression ( intervention group ) or continuation of usual medical care ( control group ) . The latter will be performed by a general practitioner according to the Dutch National Guidelines for Shoulder Problems . At inclusion , at r and omization and three , six and 12 months post-r and omization an outcome assessment will take place . The primary outcome measure is the patient-reported Shoulder Disability Question naire . The secondary outcome measures include both disease-specific and generic measures , and an economic evaluation . Treatment effects will be compared for all measurement points by using a GLM repeated measures analyses . Discussion The rationale and design of an RCT comparing arthroscopic subacromial decompression with usual medical care for subacromial impingement syndrome are presented . The results of this study will improve insight into the best moment of referral for surgery for SIS OBJECTIVE To assess the value of search ing for unpublished data by exploring the extent to which Cochrane review s include unpublished data and by evaluating the quality of unpublished trials . STUDY DESIGN AND SETTING We screened all 2,462 completed Cochrane review s published since 2000 in the Cochrane Data base of Systematic Review s Issue 3 , 2006 . In a r and om sample ( n=61 ) of 292 review s , including unpublished trials , we studied all 116 references . RESULTS Unpublished trials make up 8.8 % of all included trials in our sample . Thirty-eight percent of the " unpublished " trials have in fact been published . Allocation concealment was " unclear " or not adequate in 54.3 % and 61.3 % reported blinding . In 47.2 % reported withdrawal rates were > 20 % . Trials that were eventually published had larger mean population sizes ( P-value , 0.02 ) . Of the reported sponsors , 87.3 % were drug companies . Method ological quality and publication bias are mentioned in half of the review s and explored in a third . Quality ratings did not have consequences for pooling , because 82.8 % was included in the forest plots . CONCLUSIONS A minority of Cochrane review s include " unpublished trials " and many of these are eventually published . Truly unpublished studies have poor or unclear method ological quality . Therefore , it may be better to invest in regular updating of review s , rather than in extensive search ing for unpublished data OBJECTIVE The study investigated the effectiveness of stretching , strengthening exercises , and the scapular stabilization exercises on the pain , shoulder range of motion ( ROM ) , muscle strength , joint position sense ( JPS ) , scapular dyskinesis and quality of life ( OL ) in the patients with subacromial impingement syndrome ( SIS ) . METHODS 27 women and 13 men , mean age 51 ( 24 - 71 ) years old , were included in this study . All the patients were separated into 2 groups according to simple r and om table . Stretching and strengthening exercises were given to the group I ( n=20 ) and scapular stabilization exercises were added to the group II ( n=20 ) . The pain severity , shoulder ROM , muscle strength , JPS , lateral scapular slide test ( LSST ) , Western Ontario Rotator Cuff ( WORC ) Index were evaluated before and after treatment . Patients completed a 6-week rehabilitation program , three times a week . RESULTS The results showed that all measurements improved statistically in both groups after treatment ( p < 0.05 ) . And the improvements in the muscle strength , JPS and scapular dyskinesia were significantly different in group II ( p < 0.05 ) . CONCLUSION It is suggested that in the treatment of SIS ; scapular stabilization exercises , given with stretching and strengthening exercises , can be more effective in increasing the muscle strength , developing the JPS and decreasing the scapular dyskinesis 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 . STUDY DESIGN Nonr and omized 2 group post-test only . OBJECTIVE To compare scapular position and orientation between subjects with and without impingement syndrome . BACKGROUND Abnormal scapular motion is commonly believed to be a contributing factor to shoulder impingement syndrome . METHODS AND MEASURES Twenty nonimpaired subjects with a mean age of 34.3 ( + /- 7.5 years ) and 17 patients with impingement syndrome with a mean age of 45.8 ( + /- 11.0 ) participated . A 3-dimensional electromechanical digitizer was used to measure scapular position and orientation in 3 planes . Measurements were taken with the arm at the side , elevated in the scapular plane to horizontal , and at maximum elevation . One-way analysis of variance was used to compare nonimpaired subjects to the impingement group and the symptomatic and asymptomatic sides within the impingement group . Five scapular kinematic variables were assessed at each arm position . Orientation was described by posterior tilting angle , upward rotation angle , and internal rotation angle . Position was described by medial-lateral position and superior-inferior position and determined by the distance from the scapula centroid to the seventh cervical vertebra ( C7 ) . RESULTS During scapular plane elevation of the arm , the scapula showed a general pattern of increasing posterior-tilt angle , increasing upward-rotation angle , and decreasing internal-rotation angle in both impingement and nonimpaired groups . Also , the scapula moved to a more superior position and a slightly more medial position with increasing arm elevation . Compared to nonimpaired subjects ( 34.6 degrees + /- 9.7 ) , those with impingement demonstrated a significantly lower posterior tilting angle of the scapula in the sagittal plane ( 25.1 degrees + /- 9.1 ) . Subjects with impingement also demonstrated higher superior-inferior scapular position with maximal arm elevation ( 5.2 cm + /- 1.6 below the first thoracic vertebrae ) compared to nonimpaired subjects ( 7.5 cm + /- 1.5 ) . CONCLUSIONS These results suggest that altered scapular kinematics may be an important aspect of the impingement syndrome Background Altered muscle activity in the scapular muscles is commonly believed to be a factor contributing to shoulder impingement syndrome . However , one important measure of the muscular coordination in the scapular muscles , the timing of the temporal recruitment pattern , is undetermined . Purpose To evaluate the timing of trapezius muscle activity in response to an unexpected arm movement in athletes with impingement and in normal control subjects . Study Design Prospect i ve cohort study . Methods Muscle latency times were measured in all three parts of the trapezius muscle and in the middle deltoid muscle of 39 “ overh and athletes ” with shoulder impingement and compared with that of 30 overh and athletes with no impingement during a sudden downward falling movement of the arm . Results There were significant differences in the relative muscle latency times between the impingement and the control group subjects . Those with impingement showed a delay in muscle activation of the middle and lower trapezius muscle . Conclusion The results of this study indicate that overh and athletes with impingement symptoms show abnormal muscle recruitment timing in the trapezius muscle . The findings support the theory that impingement of the shoulder may be related to delayed onset of contraction in the middle and lower parts of the trapezius muscle BACKGROUND Shoulder pain is common in primary health care . Nevertheless , information on the outcome of shoulder disorders is scarce , especially for patients encountered in general practice . AIM To study the course of shoulder disorders in general practice and to determine prognostic indicators of outcome . METHOD For this prospect i ve follow-up study , 11 Dutch general practitioners recruited 349 patients with new episodes of shoulder pain . The participants filled out a question naire at presentation and further ones after 1 , 3 , 6 and 12 months ; these contained questions on the nature , severity and course of the shoulder complaints . The association between potential prognostic indicators and the status of shoulder complaints ( absence or presence of symptoms ) was evaluated after one and 12 months of follow-up . RESULTS After one month , 23 % of all patients showed complete recovery ; this figure increased to 59 % after one year . A speedy recovery seemed to be related to preceding overuse or slight trauma and early presentation . A high risk of persistent or recurrent complaints was found for patients with concomitant neck pain and severe pain during the day at presentation . CONCLUSION A considerable number of patients ( 41 % ) showed persistent symptoms after 12 months . It may be possible to distinguish patients who will show a speedy recovery from those with a high risk of long-st and ing complaints by determining whether there is a history of slight trauma or overuse , an early presentation or an absence of concomitant neck pain This paper describes PEDro , the Physiotherapy Evidence Data base . PEDro is a web-based data base of r and omized controlled trials and systematic review s in physiotherapy . It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro . The data base contains bibliographic details and abstract s of most English- language r and omized trials and systematic review s in physiotherapy , and of many trials and review s in other language s. Trials on the data base are rated on the basis of their method ological quality so that users of the data base can quickly identify trials of high quality . Trials and systematic review s are extensively indexed to facilitate search ing . PEDro provides an important information re source to support evidence -based clinical practice STUDY DESIGN R and omized controlled trial . OBJECTIVE To evaluate the effects of an exercise protocol , with and without manual therapy , on scapular kinematics , function , pain , and mechanical sensitivity in individuals with shoulder impingement syndrome . BACKGROUND Stretching and strengthening exercises have been shown to effectively decrease pain and disability in individuals with shoulder impingement syndrome . There is still conflicting evidence regarding the efficacy of adding manual therapy to an exercise therapy regimen . METHODS Forty-six patients were assigned to 1 of 2 groups , one of which received a 4-week intervention of stretching and strengthening exercises ( exercise alone ) and the other the same intervention , supplemented by manual therapy targeting the shoulder and cervical spine ( exercise plus manual therapy ) . All outcomes were measured preintervention and postintervention at 4 weeks . Outcome measures were scapular kinematics in the scapular and sagittal planes during arm elevation , function as determined through the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire , pain as assessed with a visual analog scale , and mechanical sensitivity as assessed with pressure pain threshold . RESULTS Independent of the intervention group , small , clinical ly irrelevant changes in scapular kinematics were observed postintervention . A significant group-by-time interaction effect ( P = .001 ) was found for scapular anterior tilt during elevation in the sagittal plane , with a 3.0 ° increase ( 95 % confidence interval [ CI ] : -1.5 ° , 7.5 ° ) relative to baseline in the exercise-plus-manual therapy group compared to a decrease of 0.3 ° ( 95 % CI : -4.2 ° , 4.8 ° ) in the exercise-alone group . Pain , mechanical sensitivity , and the DASH score improved similarly for both groups by the end of the intervention period . CONCLUSION Adding manual therapy to an exercise protocol did not enhance improvements in scapular kinematics , function , and pain in individuals with shoulder impingement syndrome . The noted improvements in pain and function are not likely explained by changes in scapular kinematics OBJECTIVES Evidence has emerged supporting the value of loaded exercises for rotator cuff tendinopathy but there are barriers that might prevent implementation of this intervention in the real-world . The purpose of this study was to explore these potential barriers with participants involved in a pilot r and omised controlled trial ( RCT ) investigating a self-managed loaded exercise intervention . DESIGN A qualitative study within the framework of a mixed methods design . Data were collected using individual interviews and analysed using the framework method . SETTING One private physiotherapy clinic in northern Engl and . PARTICIPANTS Six patients and two physiotherapists were purposively sample d from those allocated to the self-managed exercise group within the RCT . RESULTS Three themes were generated : ( 1 ) Expectations and preferences , ( 2 ) characteristics of an unsuccessful outcome , ( 3 ) characteristics of a successful outcome . Most patients expressed expectations contrary to the philosophy of a self-managed approach . But this did not serve as a barrier when the intervention was offered within a positive and supporting environment where patients understood the reasons for undertaking the exercise , effectively self-monitored and engaged with pro-active follow-up . An early and appreciable response to therapy was also a key factor influencing continuing engagement with the exercise programme . CONCLUSION With certain caveats including the need to recognise and respond to individual characteristics , implement effective knowledge translation strategies and the need to engage with appropriately timed pro-active follow-up , the potential to implement programmes of self-managed loaded exercise for patients with rotator cuff tendinopathy in the real-world and in further research studies appears feasible but challenging |
458 | 27,749,741 | No significant improvements in lean mass with WBVT were found in postmenopausal women .
In addition , there was no significant difference in lean mass between WBVT and control postmenopausal women .
Conclusions : This meta- analysis demonstrated that WBVT alone may not be a sufficient stimulus to increase lean mass in postmenopausal women . | Objective : The purpose of the present systematic review and meta- analysis was to evaluate published , r and omized controlled trials that investigated the effects of whole-body vibration training ( WBVT ) on lean mass in postmenopausal women . | To assess age and gender differences in muscle strength , isometric , concentric ( Con ) , and eccentric ( Ecc ) peak torque was measured in the knee extensors at a slow ( 0.52 rad/s ) and fast ( 3.14 rad/s ) velocity in 654 subjects ( 346 men and 308 women , aged 20 - 93 yr ) from the Baltimore Longitudinal Study of Aging . Regression analysis revealed significant ( P < 0.001 ) age-related reductions in Con and Ecc peak torque for men and women at both velocities , but no differences were observed between the gender groups or velocities . Age explained losses in Con better than Ecc peak torque , accounting for 30 % ( Con ) vs. 19 % ( Ecc ) of the variance in men and 28 % ( Con ) vs. 11 % ( Ecc ) in women . To assess age and gender differences in the ability to store and utilize elastic energy , the stretch-shortening cycle was determined in a subset of subjects ( n = 47 ) . The older women ( mean age = 70 yr ) showed a significantly greater enhancement in the stretch-shortening cycle , compared with men of similar age ( P < 0.01 ) and compared with younger men and women ( each P < 0.05 ) . Both men and women showed significant declines in muscle quality for Con peak torque ( P < 0.01 ) , but no gender differences were observed . Only the men showed a significant decline in muscle quality ( P < 0.001 ) for Ecc peak torque . Thus both men and women experience age-related losses in isometric , Con , and Ecc knee extensor peak torque ; however , age accounted for less of the variance in Ecc peak torque in women , and women tend to better preserve muscle quality with age for Ecc peak torque . In addition , older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men To determine whether 10 weeks of whole-body vibration ( WBV ) training has a significant effect on strength , muscle mass , muscle power , and mobility in older women , 26 subjects were r and omly assigned to a WBV training group ( n=13 ; mean age 79 years ) and a control ( CON ) group ( n=13 ; mean age 76 years ) . Maximal voluntary isometric contraction ( MVIC ) increased 38.8 % in the WBV group , without changes in the CON group . Electromyographic activity of the vastus medialis ( VM ) , the vastus lateralis , and the biceps femoris ( BF ) did not change in either group . Thigh muscle cross-sectional area increased significantly after training in VM ( 8.7 % ) and BF ( 15.5 % ) . Muscle power at 20 % , 40 % , and 60 % MVIC decreased from pre-test to post-test in the CON group ; however , WBV training prevented the decrease in the WBV group . Consequently , mobility , measured by the Timed Up and Go test , increased significantly after training ( 9.0 % ) only in the WBV group . Ten weeks of lower limb WBV training in older women produces a significant increase in muscle strength induced by thigh muscle hypertrophy , with no change in muscle power . The adaptations to WBV found in the present study may be of use in counteracting the loss of muscle strength and mobility associated with age-induced sarcopenia This study examined the correlations between isokinetic muscle strength of knee and elbow flexors and extensors with vertebral and femoral bone mineral density in a population of 106 women between the ages of 44 and 87 years . The absolute value of muscle strength correlated significantly with bone mineral density ; muscle strength of the upper limb appeared to be more closely correlated with bone mass , while muscle strength in the lower limb was more specific for femoral mineral bone density . The most important finding that these results demonstrated was a concomitant decline in muscle strength of the upper limb and bone mineral density between the 5th and 6th decades . In contrast , they also showed a decline in muscle strength of the lower limbs after the 6th decade , occurring before the decline in bone mineral density observed between the 7th and 8th decades . From these results it would appear that other studies are required to examine the relationship between the essentially hormonal role in postmenopausal decline in muscle strength and the decline in physical activity during the senile period . These elements are important because they must be taken into account in physical exercise programmes design ed to prevent osteoporosis The aim was to study whether whole body vibration ( WBV ) combined with conventional resistance training ( CRT ) induces a higher increase in neuromuscular and hormonal measures compared with CRT or WBV , respectively . Twenty-eight young men were r and omized in three groups ; squat only ( S ) , combination of WBV and squat ( S+V ) and WBV only ( V ) . S+V performed six sets with eight repetitions with corresponding eight repetition maximum ( RM ) loads on the vibrating platform , whereas S and V performed the same protocol without WBV and resistance , respectively . Maximal isometric voluntary contraction ( MVC ) with electromyography ( EMG ) measurements during leg press , counter movement jump ( CMJ ) measures ( mechanical performance ) including jump height , mean power ( Pmean ) , peak power ( Ppeak ) and velocity at Ppeak ( Vppeak ) and acute hormonal responses to training sessions were measured before and after a 9-week training period . ANOVA showed no significant changes between the three groups after training in any neuromuscular variable measured [ except Pmean , S higher than V ( P<0.05 ) ] . However , applying t tests within each group revealed that MVC increased in S and S+V after training ( P<0.05 ) . Jump height , Pmean and Ppeak increased only in S , concomitantly with increased Vppeak in all groups ( P<0.05 ) . Testosterone increased during training sessions in S and S+V ( P<0.05 ) . Growth hormone ( GH ) increased in all groups but S+V showed higher responses than S and V ( P<0.05 ) . Cortisol increased only in S+V ( P<0.05 ) . We conclude that combined WBV and CRT did not additionally increase MVC and mechanical performance compared with CRT alone . Furthermore , WBV alone did not increase MVC and mechanical performance in spite of increased GH Beck BR , Norling TL : The effect of 8 mos of twice-weekly low- or higher intensity whole body vibration on risk factors for postmenopausal hip fracture . Objective : Whole body vibration is a potential therapy for age-related loss of musculoskeletal competence . Vibration has improved bone in animal models , but evidence in humans is limited . Relative efficacy of low- vs. high-intensity whole body vibration is also unknown . Our goal was to observe the effect of brief low- and higher intensity whole body vibration on risk factors for hip fracture in postmenopausal women . Design : We used an 8-mo r and omized controlled trial design to examine the influence of twice-weekly low-intensity whole body vibration ( 15 mins , 30 Hz , 0.3 g ) or higher intensity whole body vibration ( 2 × 3 mins , 12.5 Hz , 1 g ) on anthropometrics , bone ( whole body , hip , spine , forearm , and heel ) , muscle ( wall squat and chair rise ) , and balance ( t and em walk and single leg stance ) . Physical activity , daily calcium , and compliance were recorded . Effects were examined by repeated- measures analysis of covariance , controlling for age , height , weight , calcium , physical activity , compliance , and baseline values . Results : Forty-seven women ( 71.5 ± 9.0 yrs ) completed the trial . There were no between-group differences in any measure at 8 mos , but within-group effects were evident . Controls lost bone at the trochanter ( −6 % , P = 0.03 ) and lumbar spine ( −6.6 % , P = 0.02 ) , whereas whole body vibration groups did not . Whole body vibration subjects improved wall squat ( up to 120 % , P = 0.004 ) and chair rise performance ( up to 10.5 % , P = 0.05 ) . Conclusions : Eight mos of twice-weekly whole body vibration may reduce bone loss at the hip and spine and improve lower limb muscle function . These changes may translate to a decreased risk of falls and hip fracture PURPOSE The aim of this study was to investigate and to compare the effect of a 12-wk period of whole-body vibration training and resistance training on human knee-extensor strength . METHODS Sixty-seven untrained females ( 21.4 + /- 1.8 yr ) participated in the study . The whole-body vibration group ( WBV , N = 18 ) and the placebo group ( PL , N = 19 ) performed static and dynamic knee-extensor exercises on a vibration platform . The acceleration of the vibration platform was between 2.28 g and 5.09 g , whereas only 0.4 g for the PL condition . Vibration ( 35 - 40 Hz ) result ed in increased EMG activity , but the EMG signal remained unchanged in the PL condition . The resistance-training group ( RES , N = 18 ) trained knee extensors by dynamic leg-press and leg-extension exercises ( 10 - 20 RM ) . All training groups exercised 3x wk-1 . The control group ( CO , N = 12 ) did not participate in any training . Pre- and postisometric , dynamic , and ballistic knee-extensor strength were measured by means of a motor-driven dynamometer . Explosive strength was determined by means of a counter-movement jump . RESULTS Isometric and dynamic knee-extensor strength increased significantly ( P < 0.001 ) in both the WBV group ( 16.6 + /- 10.8 % ; 9.0 + /- 3.2 % ) and the RES group ( 14.4 + /- 5.3 % ; 7.0 + /- 6.2 % ) , respectively , whereas the PL and CO group showed no significant ( P > 0.05 ) increase . Counter-movement jump height enhanced significantly ( P < 0.001 ) in the WBV group ( 7.6 + /- 4.3 % ) only . There was no effect of any of the interventions on maximal speed of movement , as measured by means of ballistic tests . CONCLUSIONS WBV , and the reflexive muscle contraction it provokes , has the potential to induce strength gain in knee extensors of previously untrained females to the same extent as resistance training at moderate intensity . It was clearly shown that strength increases after WBV training are not attributable to a placebo effect Background : It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults . Objective : The purpose of the present study was to compare the effects of strength training ( ST ) versus power training ( PT ) on functional performance in prefrail older adults . This study was registered at clinical trials.gov as NCT00783159 . Methods : 69 community-dwelling older adults ( > 65 years ) who were prefrail according to the definition of Fried were included in a 12-week exercise program . The participants were r and omized into an ST group , a PT group and a control group . All participants were supplemented with vitamin D3 orally before entering the intervention period . The primary outcome was the global score on the Short Physical Performance Battery ( SPPB ) . Secondary outcomes were muscle power , appendicular lean mass ( aLM ) measured by dual energy X-ray absorptiometry and self-reported functional deficits ( Short Form of the Late-Life Function and Disability Instrument , SF-LLFDI ) . Results : Regarding changes in the SPPB score during the intervention , significant heterogeneity between the groups was observed ( p = 0.023 ) . In pair-wise comparisons , participants in both training groups significantly ( PT : p = 0.012 , ST : 0.009 ) increased their SPPB score ( PT : Δmean = 0.8 , ST : Δmean = 1.0 ) compared to the control group , with no statistical difference among training groups ( p = 0.301 ) . No statistical differences were found in changes in aLM ( p = 0.769 ) , muscle power ( p = 0.308 ) and SF-LLFDI ( p = 0.623 ) between the groups . Muscle power significantly increased ( p = 0.017 ) under vitamin D3 intake . Conclusions : In prefrail community-dwelling adults , PT is not superior to ST , although both training modes result ed in significant improvements in physical performance . With regard to dropout rates , ST appears to be advantageous compared to PT . The high prevalence of vitamin D3 deficiency and the slight improvement of physical performance under vitamin D3 supplementation among study participants underline the relevance of this approach in physical exercise interventions UNLABELLED High-frequency mechanical strain seems to stimulate bone strength in animals . In this r and omized controlled trial , hip BMD was measured in postmenopausal women after a 24-week whole body vibration ( WBV ) training program . Vibration training significantly increased BMD of the hip . These findings suggest that WBV training might be useful in the prevention of osteoporosis . INTRODUCTION High-frequency mechanical strain has been shown to stimulate bone strength in different animal models . However , the effects of vibration exercise on the human skeleton have rarely been studied . Particularly in postmenopausal women-who are most at risk of developing osteoporosis-r and omized controlled data on the safety and efficacy of vibration loading are lacking . The aim of this r and omized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration ( WBV ) in postmenopausal women . MATERIAL S AND METHODS Seventy volunteers ( age , 58 - 74 years ) were r and omly assigned to a whole body vibration training group ( WBV , n = 25 ) , a resistance training group ( RES , n = 22 ) , or a control group ( CON , n = 23 ) . The WBV group and the RES group trained three times weekly for 24 weeks . The WBV group performed static and dynamic knee-extensor exercises on a vibration platform ( 35 - 40 Hz , 2.28 - 5.09 g ) , which mechanically loaded the bone and evoked reflexive muscle contractions . The RES group trained knee extensors by dynamic leg press and leg extension exercises , increasing from low ( 20 RM ) to high ( 8 RM ) resistance . The CON group did not participate in any training . Hip bone density was measured using DXA at baseline and after the 6-month intervention . Isometric and dynamic strength were measured by means of a motor-driven dynamometer . Data were analyzed by means of repeated measures ANOVA . RESULTS No vibration-related side effects were observed . Vibration training improved isometric and dynamic muscle strength ( + 15 % and + 16 % , respectively ; p < 0.01 ) and also significantly increased BMD of the hip ( + 0.93 % , p < 0.05 ) . No changes in hip BMD were observed in women participating in resistance training or age-matched controls ( -0.60 % and -0.62 % , respectively ; not significant ) . Serum markers of bone turnover did not change in any of the groups . CONCLUSION These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies 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 . OBJECTIVES Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance . We tested the hypothesis that a high-velocity resistance-training program ( HI ) would increase muscle power more than a traditional low-velocity resistance-training program ( LO ) . DESIGN R and omized controlled trial . SETTING University-based human physiology laboratory . PARTICIPANTS Thirty women with self-reported dis-ability ( aged 73 + 1 , body mass index 30.1 + 1.1 kg/mn ) . INTERVENTION We conducted a r and omized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO . Training was performed three times per week , and subjects completed three sets ( 8 - 10 repetitions ) of leg press ( LP ) and knee extension ( KE ) exercises at 70 % of the one-repetition maximum ( IRM ) . MEASUREMENTS One-repetition maximum ( 1 RM ) and peak power for KE and LP . RESULTS LP and KE relative training force and total work were similar between groups ( P > .05 ) . However , HI generated significantly higher power during training sessions than LO for LP ( 3.7-fold greater , P < .001 ) and KE ( 2.1-fold greater , P < .001 ) . Although LP and KE 1RM muscle strength increased similarly in both groups asa result of the training ( P < .001 ) , LP peak power increased significantly more in HI than in LO ( 267 W vs 139 W , P < .001 ) . Furthermore , HI result ed in a significantly greater improvement in LP power at 40 % , 50 % , 60%,70 % , 80 % , and 90 % of the 1 RM than did LO ( P < .05 ) . CONCLUSIONS HI improved 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women . Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions The aims of this study were to analyze the effects of two different training protocol s-vibratory platform and multi-component training-- and to determine what kind of training creates greater adaptations on bone density and isokinetic strength of the knee extensors and the stabilizer muscles of the ankle joint in post-menopausal women . Thirty-eight women ( 59.8 ± 6.2 years ) were r and omly assigned to whole-body vibration group ( WBVG ) , multi-component training group ( MTG ) , or a control group ( CG ) . The experimental groups performed incremental training for 12 weeks , three sessions/week . Significant differences were found in total fat mass and total lean mass in the training groups . In addition , both WBVG and MTG showed significant increases in isokinetic strength for knee extensors at 60 ° ·s(-1 ) and at 270 ° ·s(-1 ) . With respect to the ankle joint , a significant increase for eversion at 60 ° ·s(-1 ) and inversion at 60 ° ·s(-1 ) was found in both training groups , and eversion at 120 ° ·s(-1 ) only in WBVG ( p = 0.012 ) . There were no significant differences between WBVG and MTG in knee and ankle strength tests . Therefore , we found significant adaptations to whole-body vibration and multi-component training in the present study . However , the improvements were similar for both groups and we can not cl aim that WBVG is better than MTG , or vice versa |
459 | 26,848,926 | Adverse events were generally poorly reported .
No evidence was available for relapse , quality of life or service use . | BACKGROUND There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds .
Among many possible c and i date s , oxidative stress may be one of the mediators of neuroprogression , grey matter loss and subsequent cognitive and functional impairment .
Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences .
They may act from directly scavenging free radicals to increasing anti-oxidative defences .
There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia .
The existing literature , however , indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia .
As such , there has been interest in developing interventions aim ed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction .
If antioxidants are to have a place in the treatment of this serious condition , the relevant and up-to- date information should be available to clinicians and investigators .
OBJECTIVES To evaluate the effect of antioxidants as add-on treatments to st and ard antipsychotic medication for improving acute psychotic episodes and core symptoms , and preventing relapse in people with schizophrenia . | Abstract Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis . Oxidative stress has also been implicated in the extrapyramidal symptoms ( EPS ) produced by haloperidol . Supporting the oxidative stress hypothesis , vitamin E ( antioxidant ) has demonstrated therapeutic efficacy in idiopathic parkinsonism . The prophylactic efficacy of vitamin E ( antioxidant ) on haloperidol-induced EPS was examined in a r and omized controlled trial . The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial . All patients received oral haloperidol 10 mg/day . The sample was equally r and omized to receive either haloperidol alone or haloperidol + vitamin E ( 3200 IU/day ) . EPS was rated at recruitment , both live and with video records , and on days 3 , 7 , 10 and 14 . Psychopathology was rated at recruitment and weekly thereafter . Vitamin E had no prophylactic effect on drug-induced EPS , though it did not interfere with the therapeutic efficacy of haloperidol It has been suggested that the extract of gingko biloba ( EGb ) may enhance the efficiency of the classic antipsychotic haloperidol in patients with chronic schizophrenia , especially on positive symptoms , and reduce serum superoxide dismutase ( SOD ) levels . Therefore , we decided to evaluate the therapeutic effect of EGb and to examine the effect of it on the levels of antioxidant enzymes in schizophrenic patients on olanzapine treatment . We hypothesized that EGb would have the beneficial effects on schizophrenic symptoms and might cause reductions in antioxidant enzymes . The subjects were r and omly assigned to the two groups : olanzapine plus EGb ( group I ) ( n=15 ) and olanzapine alone ( group II ) ( n=14 ) . The patients were evaluated at baseline and at week 8 with respect to the Positive and Negative Syndrome Scale ( PANSS ) , serum SOD , catalase ( CAT ) , and glutathion peroxidase ( GPX ) levels . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . At the evaluation of week 8 , a significant difference in mean Scale for the Assessment of Postive Symptoms ( SAPS ) scores but not in Scale for the Assessment of Negative Symptoms scores between groups was found . Total patients had statistically significant higher serum SOD , CAT and GPX levels compared to control groups at baseline . At 8 weeks , there were significant differences in the mean decrease in SOD and CAT levels but not in GPX levels between treatment groups . The changes in SOD and CAT levels were correlated with the change in SAPS in group I , but not in the group II . The present study supported the findings of the previous study demonstrating that EGb might enhance the efficiency of antipsychotic in patients with schizophrenia , particularly on positive symptoms of the disorder OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia . However , long-term treatment with antipsychotics is associated with a variety of movement disorders , the most disabling of which is tardive dyskinesia ( TD ) , which occurs in up to 50 % of patients hospitalized with chronic schizophrenia . The pathophysiology of TD is still unclear and no definite treatment exists . Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated . The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus . Thus , it may have a beneficial effect for both the treatment and prevention of TD . METHODS Using a double-blind , placebo-controlled , crossover study , we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD . The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . RESULTS The decrease ( mean + /- SD ) in AIMS score was 2.45 + /- 1.92 for the melatonin and 0.77 + /- 1.11 for the placebo treatment groups ( P<.001 ) . No adverse events or side effects were noted . CONCLUSION This is the first clinical evidence for efficacy of melatonin in the treatment of TD Adherence to prescribed medications is believed to be a major problem in medicine . However , actual medication taking behaviour is rarely measured as no reliable objective measures of adherence are available . 50 mg of riboflavin administered at night could be reliably detected in urine , under UV light , for the next 18 - 24 h. The ability of 20 schizophrenic out patients to adhere to a once-a-night dosage was studied by dispensing riboflavin or placebo in a r and om sequence and testing the urine for UV fluorescence the next day . The majority of patients ( 80 % ) had errors between 40 - 80 % of the times tested . Only age and sex predicted the level of adherence . Clinicians were very poor predictors of the error rates in their patients The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba ( EGb ) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase ( SOD ) levels . Eighty-two patients with chronic refractory schizophrenia were studied . Forty-three patients were treated with haloperidol plus extract of ginkgo biloba ( group 1 ) , and 39 received haloperidol plus placebo ( group 2 ) . SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers . Therapeutic efficiency was equated with a change in clinical rating scores assessed by st and ardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms ( SANS ) over this period . Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments ; those in group 2 improved significantly only as shown by scores on SANS . SOD levels before treatment in all patients were significantly higher than those in healthy controls ; after treatment , the SOD level decreased significantly in group 1 but not in group 2 . These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia , especially on their positive symptoms , and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia BACKGROUND Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described . Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome . This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia . OBJECTIVE To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition . DESIGN Longitudinal , r and omized , controlled , multisite , double-blind study . Patients treated and followed up for up to 104 weeks . Neurocognitive and magnetic resonance imaging ( MRI ) assessment s performed at weeks 0 ( baseline ) , 12 , 24 , 52 , and 104 . Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI , psychopathologic , and neurocognitive outcomes . SETTING Fourteen academic medical centers ( United States , 11 ; Canada , 1 ; Netherl and s , 1 ; Engl and , 1 ) . PARTICIPANTS Patients with first-episode psychosis ( DSM-IV ) and healthy volunteers . INTERVENTIONS R and om allocation to a conventional antipsychotic , haloperidol ( 2 - 20 mg/d ) , or an atypical antipsychotic , olanzapine ( 5 - 20 mg/d ) . MAIN OUTCOME MEASURES Brain volume changes assessed by MRI . RESULTS Of 263 r and omized patients , 161 had baseline and at least 1 postbaseline MRI evaluation . Haloperidol-treated patients exhibited significant decreases in gray matter volume , whereas olanzapine-treated patients did not . A matched sample of healthy volunteers ( n = 58 ) examined contemporaneously showed no change in gray matter volume . CONCLUSIONS Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes . Haloperidol was associated with significant reductions in gray matter volume , whereas olanzapine was not . Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated . The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia OBJECTIVE The authors ' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in out patients with schizophrenia who had negative symptoms of moderate or greater severity . METHOD A 12-week , double-blind , placebo-controlled , multicenter trial of oral selegiline augmentation of antipsychotic medication was carried out . Out patients were chosen who did not manifest severe positive symptoms at baseline , who did not meet criteria for coexisting major depression , and who had been maintained on a stable regimen of antipsychotic medication . RESULTS Negative symptoms were found to be significantly more improved in the patients who received selegiline , and global improvement scores reinforced the impression that selegiline augmentation was beneficial . CONCLUSIONS These findings support further investigation of low-dose selegiline augmentation of antipsychotic medication in out patients with schizophrenia who have at least a moderate burden of negative symptoms The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Abstract : Free radicals may be involved in the pathogenesis of tardive dyskinesia ( TD ) . Vitamin E , a free radical scavenger , has been reported to improve symptoms of TD . The present study was design ed to replicate this finding in a group of Chinese patients with TD , and to examine the effect of vitamin E treatment on blood superoxide dismutase ( SOD ) , a critical enzyme in the detoxification of free radicals . Forty-one in patients with TD completed a double-blind , placebo-controlled , parallel-group study of vitamin E. Twenty-two of the patients were r and omly assigned to receive a fixed dose of 1200 IU/d vitamin E , and 19 were assigned to a placebo for 12 weeks . Patients were assessed primarily using the Abnormal Involuntary Movement Scale ( AIMS ) at baseline , weeks 6 and 12 . Blood SOD levels were measured by radioimmunometric assay before and after treatment . The results showed that the reduction in AIMS score from baseline was significantly higher with vitamin E treatment compared with placebo ( 45.9 % vs. 4.3 % ) . Blood SOD levels were significantly increased after treatment with vitamin E ( P = 0.001 ) , but no change with placebo treatment ( P < 0.05 ) . These results support earlier findings of the efficacy of vitamin E in the treatment of TD . Moreover , the efficacy of vitamin E may be due to its ability to increase SOD level , which may reduce oxidative injure in tardive dyskinesia The authors compared vitamin E with placebo in a double-blind r and omized crossover study of 27 patients with tardive dyskinesia . Each treatment period lasted for 6 weeks . Vitamin E showed no differences from placebo in the treatment of tardive dyskinesia There is a large amount of data showing that adenosine plays a role opposite to dopamine in the brain . Adenosine agonists and antagonists produce behavioral effects similar to dopamine antagonists and dopamine agonists , respectively . Allopurinol , a well-known hypouricemic drug that inhibits xantine oxidase , has been used as an add-on drug in the treatment of poorly responsive schizophrenic patients . Indeed , the neuropsychiatric effects of allopurinol in schizophrenia have been suggested to be secondary to its inhibitory effect of purine degradation , enhancing adenosinergic activity . The purpose of the present investigation was to assess the efficacy of allopurinol as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial . Eligible participations in the study were 46 patients with schizophrenia . All patients were in patients and were in the active phase of the illness , and met DSM-IV criteria for chronic schizophrenia . Patients were allocated in a r and om fashion , 23 to haloperidol 15 mg/day plus allopurinol 300 mg/day and 23 to haloperidol 15 mg/day plus placebo . Although both protocol s significantly decreased the score of the positive , negative and general psychopathological symptoms over the trial period , the combination of haloperidol and allopurinol showed a significant superiority over haloperidol alone in the treatment of positive symptoms , general psychopathology symptoms as well as PANSS total scores . The means of Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the allopurinol group over the trial , and the differences were significant in weeks 6 and 8 . A significant difference was observed between the overall mean biperiden dosages in two groups . The results of this study suggest that allopurinol may be an effective adjuvant agent in the management of patients with chronic schizophrenia . Nevertheless , results of larger controlled trials are needed , before recommendations for a broad clinical application can be made BACKGROUND Low nighttime levels of melatonin have been demonstrated in patients with insomnia , and melatonin has been shown to have hypnotic properties in some groups of such subjects . Low melatonin levels have also been observed in patients with schizophrenia ; however , there is little literature on the efficacy of exogenous melatonin in treating insomnia associated with schizophrenia . METHOD Stable DSM-IV schizophrenic out patients ( N = 40 ) with initial insomnia of at least 2 weeks ' duration were r and omly assigned to augment their current medications with either flexibly dosed melatonin ( 3 - 12 mg/night ; N = 20 ) or placebo ( N = 20 ) . By use of a question naire , double-blind assessment s of aspects of sleep functioning were obtained daily across the next 15 days . The study was conducted between March and December 2002 . RESULTS The modal stable dose of melatonin was 3 mg . Relative to placebo , melatonin significantly improved the quality and depth of nighttime sleep , reduced the number of nighttime awakenings , and increased the duration of sleep without producing a morning hangover ( p < .05 ) . Subjectively , melatonin also significantly reduced sleep-onset latency , heightened freshness on awakening , improved mood , and improved daytime functioning ( p < .05 ) . CONCLUSION Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia . Melatonin could be considered for patients in whom conventional hypnotic drug therapy or higher sedative antipsychotic drug doses may be problematic A double-blind , placebo-controlled crossover study was undertaken in 10 neuroleptic-treated male schizophrenic out patients to assess the effect of coadministration of selegiline 15 mg/day for 3 weeks on their sexual dysfunction . Selegiline was not found to be effective in improving any domain of sexual functioning despite a significant decrease in prolactin levels ( P < 0.05 ) . This study emphasizes the complex nature of sexual dysfunction in schizophrenic-treated patients and the need for placebo-controlled trials for this condition OBJECTIVE It has been reported that selegiline , a Selective Monoamine Oxidase Inhibitor B ( MAOI-B ) , at low doses would be helpful for treating negative symptoms in schizophrenia . Nevertheless , the results are contradictory so far . This study was design ed to investigate the effect of selegiline added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in an 8 week , double blind and r and omized clinical trial . METHODS Eligible participants in this study were 40 patients with chronic schizophrenia . All patients were in patients and were in the active phase of the illness , and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion , 20 to risperidone 6 mg/day plus selegiline 10 mg/day ( 5 mg bid ) and 20 to risperidone 6 mg/day plus placebo . The principal measure of the outcome was Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Although both protocol s significantly decreased the score of the positive , negative , and general psychopathological symptoms over the trial period , the combination of risperidone and selegiline showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores . CONCLUSION The present study indicates selegiline as a potential adjunctive treatment strategy for the negative symptoms of schizophrenia . Nevertheless , results of larger controlled trials are needed before recommendation for a broad clinical application can be made BACKGROUND Tardive dyskinesia is a severe and disabling side effect of conventional antipsychotic treatment , with incidence rates reaching a high of 50 % in chronically institutionalized population s. On the basis of recent studies showing some benefit of antioxidants , we evaluated the effect of melatonin , the most potent naturally occurring antioxidant , on tardive dyskinesia in patients with chronic schizophrenia . METHOD Nineteen patients ( 8 men , 11 women ) , aged a mean + /- SD 74.0+/-9.5 years with chronic DSM-IV schizophrenia of 31.3+/-7.0 years ' duration , were r and omly assigned in a double-blind , placebo-controlled , crossover trial to receive slow-release melatonin , 2 mg/day , or placebo for 4 weeks . After a 2-week washout period , the patients were switched to the other treatment arm for an additional 4 weeks . The Abnormal Involuntary Movement Scale ( AIMS ) was administered at baseline , 4 weeks , 6 weeks , and 10 weeks . Regular administration of antipsychotic and other medications was kept unchanged throughout the study . RESULTS Mean AIMS scores did not change significantly from baseline in either treatment arm . All patients completed the study , and there were no side effects or adverse events . CONCLUSION Supraphysiologic doses of melatonin do not positively affect tardive dyskinesia . Considering that melatonin is a safe drug , further studies are needed of higher doses and in patients with shorter disease duration before its use in the treatment of tardive dyskinesia is ruled out The goal of this study was to determine whether selegiline ( L-deprenyl ) , a selective monoamine oxidase B inhibitor and antioxidant , would improve neuroleptic-induced tardive dyskinesia ( TD ) . Thirty-three patients with TD were r and omly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1 , 2 , 4 , and 6 for TD , parkinsonism , akathisia , depression , and positive and negative symptoms . Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination . Twenty-eight subjects completed at least 1 week of treatment ; all five dropouts were receiving selegiline . When baseline score and gender were controlled , the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group . The two treatment groups did not differ in any other outcome measure . Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial . This may be the result of the dopamine agonist effects associated with selegiline Rationale Several investigators implicated role of free radical-mediated pathology in schizophrenia . No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia . Objective The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde ( MDA ) , plasma ascorbic acid levels , and brief psychiatric rating scale ( BPRS ) score in schizophrenic patients . Method Forty schizophrenic patients participated in a prospect i ve , double-blind , placebo-controlled , noncrossover , 8-week study . The patients with schizophrenia were divided r and omly into placebo and vitamin C group of 20 each . Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye , respectively . Result Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients . These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics . BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo . Conclusion Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels , reduces oxidative stress , and improves BPRS score , hence both the drugs in combination can be used in the treatment of schizophrenia BACKGROUND Several studies have found that alpha-tocopherol ( vitamin E ) can effectively treat tardive dyskinesia ( TD ) . A limitation of these trials is their short treatment duration s ( maximum of 12 weeks ) , which do not allow us to address the effects of long-term treatment . METHODS To participate , patients had to have TD and be on stable oral medications . The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E ( 1600 IU per day ) or placebo . RESULTS Using the Abnormal Involuntary Movements Scale ( AIMS ) score ( sum of items # 1 - 7 ) to measure TD severity , the study found a significant difference ( 3 points ) in mean AIMS scores , in favor of vitamin E , starting at 10 weeks of treatment and continuing through the full 36 weeks . We used linear mixed-effects regression to quantify the impact of several covariates , and found that treatment assignment . TD duration , and chlorpromazine equivalents had significant effects on decreasing the AIMS score . CONCLUSIONS The study 's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks . These findings are in direct contrast to those of VA Cooperative Study # 394 , a much larger , long-term , multi-site study , conducted by many of the same investigators , in which Vitamin E was not superior to placebo OBJECTIVE Pregnenolone ( PREG ) and dehydroepi and rosterone ( DHEA ) are reported to have a modulatory effect on neuronal excitability , synaptic plasticity , and response to stress ; they are associated with mood regulation and cognitive performance . We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder . METHOD This 8-week , double-blind , r and omized , placebo-controlled , 2-center study compared 30 mg/d of PREG ( PREG-30 ) , 200 mg/d of PREG ( PREG-200 ) , 400 mg/d of DHEA , and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients ( DSM-IV ) . The data were collected from February 2005 until June 2007 . The outcome measures were symptomatic and neurocognitive changes , functioning , and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale . Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters . RESULTS Compared with subjects who received placebo , those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects ( EPS ) and improvement in attention and working memory performance , whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period . The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA , while EPS improved more in subjects treated with DHEA than in patients receiving placebo . Negative symptoms and akathisia were not significantly benefited by any treatment . The administration of PREG and DHEA was well tolerated . CONCLUSIONS Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients . Further double-blind controlled studies are needed to investigate the clinical benefit of pregnenolone augmentation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00174889 OBJECTIVE Vitamin E ( alpha-tocopherol ) , a free-radical scavenger , has been reported to improve symptoms of tardive dyskinesia . The authors attempted to replicate this finding under more controlled conditions in a larger study group . METHOD Fifteen in patients and six out patients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind , placebo-controlled crossover study . Abnormal Involuntary Movement Scale ( AIMS ) examinations of these patients were videotaped and rated independently by two trained raters . Levels of neuroleptic medication and vitamin E were measured during both treatment periods . Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis . RESULTS Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo . For all 18 patients , there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo . In agreement with previous studies , however , the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo . There were no changes in neuroleptic levels during vitamin E treatment . CONCLUSIONS Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less . This effect was not due to an increase in blood levels of neuroleptic medications BACKGROUND Treatment-resistant subthreshold depression is a major problem in bipolar disorder . Both depression and bipolar disorder are complicated by glutathione depletion . We hypothesized that treatment with N-acetyl cysteine ( NAC ) , a safe , orally bioavailable precursor of glutathione , may improve the depressive component of bipolar disorder . METHODS A r and omized , double-blind , multicenter , placebo-controlled study of individuals ( n = 75 ) with bipolar disorder in the maintenance phase treated with NAC ( 1 g twice daily ) adjunctive to usual medication over 24 weeks , with a 4-week washout . The two primary outcomes were the Montgomery Asberg Depression Rating Scale ( MADRS ) and time to a mood episode . Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status , quality of life , and functioning . RESULTS NAC treatment caused a significant improvement on the MADRS ( least squares mean difference [ 95 % confidence interval ] : -8.05 [ -13.16 , -2.95 ] , p = .002 ) and most secondary scales at end point . Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS . Improvements were lost after washout . There was no effect of NAC on time to a mood episode ( log-rank test : p = .968 ) and no significant between-group differences in adverse events . Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts . CONCLUSIONS NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder OBJECTIVE To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia , with the objective of increasing the endogenous pool of purines , including the neuro-modulator adenosine . METHOD A double-blind , placebo-controlled , crossover clinical trial of add-on allopurinol ( 300 mg b.i.d . ) for poorly responsive schizophrenia or schizoaffective disorder ( DSM-IV criteria ) was conducted . Thirty-five patients were enrolled , of whom 22 completed the 12 weeks of the study . Eighteen of these patients also completed a P50 evoked potential evaluation . RESULTS Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative , and general scores , particularly for positive symptoms compared with baseline and with placebo phase . Nine patients improved more than 20 % in PANSS total score during allopurinol treatment , whereas none responded in the placebo phase . Responders had a shorter duration of illness than nonresponders . P50 auditory sensory gating failed to improve with allopurinol treatment . CONCLUSIONS Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia , especially for refractory positive symptoms OBJECTIVE To investigate if adjunctive allopurinol reduces symptoms in schizophrenia out patients with persistent symptoms despite adequate pharmacotherapy . METHOD N=59 schizophrenia out patients were r and omly assigned to receive adjunctive allopurinol 300 mg bid or identical-looking placebo for 8 weeks after a 2-week placebo run-in . Symptoms were assessed biweekly . RESULTS A total of n=51 patients completed the trial . Including all n=59 r and omized patients , a total of 4 of 31 in the allopurinol group and 0 of 28 in the placebo group had at least a 20 % reduction in total PANSS score at the final study visit ( chi-square=3.88 , p=.049 ) . Among the n=51 completers , individuals in the allopurinol group rated themselves as more improved than did those in the placebo group ( z=-2.24 , p=.025 ) . The allopurinol medication was well tolerated and there were not any adverse events attributed to the study medication . CONCLUSIONS Allopurinol may be an effective adjunctive medication for some patients with persistent schizophrenia Changes in serum creatine phosphokinase have been associated with exacerbation of tardive dyskinesia . Vitamin E , a drug suggested to be effective in the treatment of tardive dyskinesia , has been implicated as a possible cause of increased creatine phosphokinase levels . Ten patients with long-term tardive dyskinesia were treated with vitamin E in a double-blind , placebo-controlled crossover study . Vitamin E blood levels and creatine phosphokinase serum levels were monitored at various phases during the study . There were no significant differences between vitamin E and placebo treated patients in their abilities to affect tardive dyskinesia or to influence creatine phosphokinase levels . These data do not support the hypothesis that administration of vitamin E may alter creatine phosphokinase levels in patients with long-term tardive dyskinesia BACKGROUND This study was design ed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia ( TD ) . METHOD Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were r and omly assigned to receive 800 IU b.i.d . of vitamin E and 18 were assigned to placebo for 2 months . Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder . Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale ( m AIMS ) , Simpson-Angus Scale for extrapyramidal side effects , and Brief Psychiatric Rating Scale . Additionally , a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia . RESULTS There was a significant reduction of dyskinesia in the vitamin E group , but not the placebo group , on both the m AIMS and the instrumental assessment s. The overall reduction in m AIMS in the active group was 24 % , with 5 ( 29 % ) of 17 patients demonstrating greater than 33 % reduction in score . There was a greater reduction in mean m AIMS score ( 35 % ) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction ( 11 % ) in patients with TD for greater than 5 years . No change was observed in parkinsonism . In the patients with schizophrenia , there was a reduction in positive symptoms after vitamin E. CONCLUSION Vitamin E appears to be effective in reducing the severity of TD , especially in patients who have had TD for 5 years or less The aim of our study was to provide further information as to the efficacy of vitamin E for the management of tardive dyskinesia Augmentation of dopaminergic neurotransmission has been suggested as a treatment strategy for negative symptoms of schizophrenia . On the basis of open studies that reported the potential benefit of deprenyl ( selegiline ) as augmentation to antipsychotic treatment , this double-blind , controlled study was design ed to further address this question . Sixteen schizophrenic patients with predominately negative symptoms , manifesting clinical stability on maintenance antipsychotic treatment , were r and omly assigned to receive either deprenyl 15 mg/day or placebo in addition to their antipsychotic treatment for 8 weeks . Clinical follow-up and ratings were done during this period and for 8 more weeks after deprenyl discontinuation . Both groups showed a statistically significant but clinical ly marginal improvement over the 8 weeks of deprenyl or placebo treatment . This improvement was abolished during the postdiscontinuation follow-up period . Deprenyl at a dose of 15 mg/day did not offer therapeutic benefit in our patients . A significant placebo effect was observed , which may be the result of increased patient-doctor contact during the study OBJECTIVE Free radicals may be involved in the pathogenesis of tardive dyskinesia ( TD ) . Extract of Ginkgo biloba ( EGb ) is a potent antioxidant possessing free radical-scavenging activities . The aim of the study was to evaluate the efficacy of EGb-761 , a st and ardized extract given in capsule form , in treating TD in schizophrenia patients . METHOD In patients with DSM-IV-diagnosed schizophrenia and TD ( n = 157 ) in a mainl and China Veterans Affairs psychiatric hospital were r and omly assigned to 12 weeks of treatment with either EGb-761 , 240 mg/d ( n = 78 ) or a placebo ( n = 79 ) in a double-blind manner . Primary outcome measures were ( 1 ) change from baseline in the Abnormal Involuntary Movement Scale ( AIMS ) score and ( 2 ) proportion of patients with a ≥ 30 % reduction in their AIMS total score at week 12 . Secondary outcome measures included the Positive and Negative Syndrome Scale ( PANSS ) and cognitive performance as measured by the Continuous Performance Test-37 Version and the 3-card Stroop task . Patients were recruited for the study between December 2006 and May 2007 . RESULTS Of the 157 patients who were r and omly assigned , 152 ( 96.8 % ) completed the study . EGb-761 treatment significantly decreased the AIMS total score in patients with TD compared to those who were given a placebo ( 2.13 ± 1.75 vs -0.10 ± 1.69 ; P < .0001 ) , with 40 ( 51.3 % ) and 4 ( 5.1 % ) patients achieving response in the EGb-761 and placebo treatment groups , respectively . There were no between-group differences in the PANSS total score or cognitive measures from baseline to week 12 . CONCLUSIONS EGb-761 appears to be an effective treatment for reducing the symptoms of TD in schizophrenia patients , and improvement may be mediated through the well-known antioxidant activity of this extract . TRIAL REGISTRATION clinical trials.gov identifier : NCT00672373 OBJECTIVE The authors studied the effects of vitamin E treatment of tardive dyskinesia ; earlier studies have produced contradictory results . METHOD Twenty-eight patients with tardive dyskinesia were treated in a double-blind , parallel-group comparison study of 8 - 12 weeks of treatment with vitamin E ( 1600 IU/day ) or matching placebo capsules . RESULTS The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo . CONCLUSIONS These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia Eight subjects with persistent tardive dyskinesia were treated with vitamin E and placebo in a r and omized , double-blind crossover study . Their mean score on the Abnormal Involuntary Movement Scale ( AIMS ) was significantly lower after treatment with vitamin E than after placebo administration : Psychogeriatric in patients were treated with a B-complex and C vitamin preparation ( Albee with C ) for six weeks in a double-blind study . ( Total N = 132 . ) They were rated on the MIBS , a new inpatient behavior form that involves 11 factored scales . One clinical ly and statistically significant finding emerged : there was a striking decrease in pathologic manifestations on the MIBS Excitement scale for a non-schizophrenic subgroup of the vitamin-treated sample compared to the placebo sample . Implication s of this finding are discussed in terms of a detailed examination of the Excitement scale and in terms of a literature review of the effects of vitamin therapy on the behavior of psychogeriatric patients Objectives Despite the burden of negative symptoms on quality of life in schizophrenic patients , no completely effective treatment has been developed to address such symptoms yet . Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia , and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia . N-Acetylcysteine ( NAC ) is a potent antioxidant with neuroprotective properties . This study aim ed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia . Material s and Methods In this r and omized , double-blind , placebo-controlled , parallel-group study , 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale ( PANSS ) were enrolled in the active phase of their illness . The participants were equally r and omized to receive NAC ( up to 2 g/d ) or placebo , in addition to risperidone ( up to 6 mg/d ) for 8 weeks . The participants were rated using PANSS every 2 weeks , and the decrease of PANSS negative subscale score was considered as our primary outcome . Results By the study end point , NAC-treated patients showed significantly greater improvement in the PANSS total ( P = 0.006 ) and negative subscale ( P < 0.001 ) scores than that in the placebo group , but this difference was not significant for positive and general psychopathology subscales . There was no significant difference between the 2 groups in the frequency of adverse effects . Conclusions NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials BACKGROUND Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia . Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia . The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba ( EGb ) plus haloperidol in chronic , treatment-resistant in patients with schizophrenia . METHOD One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind , placebo-controlled , parallel-group study of EGb plus haloperidol . Fifty-six of the patients were r and omly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol , 0.25 mg/kg/day , and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks . Patients were assessed using the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment of Negative Symptoms ( SANS ) , and the Scale for the Assessment of Positive Symptoms ( SAPS ) at baseline , week 6 , and week 12 and the Treatment Emergent Symptom Scale ( TESS ) for side effects at week 12 . RESULTS There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment ( p < .05 ) . However , a significant reduction in total SAPS and SANS scores was noted in the EGb group ( p < .05 ) , but not in the placebo group . There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment ( p < .05 ) . Of those treated with EGb plus haloperidol , 57.1 % were rated as responders as compared with only 37.7 % of those receiving placebo plus haloperidol when assessed by the SAPS ( chi2 = 4 . 111 , p = .043 ) . After 12 weeks of treatment , TESS subscore 1 ( behavioral toxicity ) and subscore 3 ( symptoms of nerve system ) were significantly decreased in the EGb group compared with the placebo group ( p < .05 ) . CONCLUSION EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects In a double-blind placebo controlled trial , the efficacy of Vitamin E in the treatment of tardive dyskinesia ( TD ) was studied in 32 patients . After a two week wash-out phase a baseline ( 0 week ) TD rating was assessed on the tardive dyskinesia rating scale ( TDRS ) . Subsequently , the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E ( 600 mg ) and 15 patients received identical placebo capsules . In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week . All patients were rated on the TDRS at the end of each week . The baseline TDRS score in the vitamin E group was significantly higher than the placebo group . This was hence adjusted and the results were then subjected to analysis of co- variance . The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group ( p = 0.03 ) It is estimated that approximately 20 % of patients receiving treatment with antipsychotic drugs develop tardive dyskinesia ( Feltner and Hertzman 1993 ) . Tardive dyskinesia rarely appears with less than 6 months of neuroleptic therapy ; however , its incidence increases substantially following treatment after 1 year . Many cases are persistent , often irreversible , and may result in social and physiological impairment . Lohr ( 1991 ) hypothesizes that metabolism of catecholamines results in the formation of neurotoxic compounds that adversely affect neurotransmission and cause damage to cellular processes . Vitamin E , a free-radical scavenging agent with antioxidant properties , could neutralize this damaging effect and therefore has been suggested as an effective treatment for tardive dyskinesia . Dabiri et a1 ( 1994 ) , in a study of 11 patients , suggest that vitamin E improved tardive dyskinesia as measured by reduction in Abnormal Involuntary Movement Scale ( AIMS ) . Adler et a1 ( 1993 ) reported a mean reduction of 32.5 % in AIMS scores in 28 patients . On the other h and , Egan et al ( 1992 ) , in 16 patients , reported only a minor beneficial effect in selected patients , while Shriqui et a1 ( 1992 ) reported no differences between vitamin E and placebo in 27 patients with tardive dyskinesia . The aim of our study was to provide further information regarding the efficacy of vitamin E in the mitigation of long-term tardive dyskinesia in a predominantly older population |
460 | 18,727,715 | There were no significant differences in mortality rates . | BACKGROUND Fast track surgery accelerates recovery , reduces morbidity and shortens hospital stay .
It is unclear what the effects are of laparoscopic or open surgery within a fast track programme .
The aim of this systematic review was to review the existing evidence . | The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing a wide range of colorectal procedures BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes Background : To evaluate the feasibility of a fast-track ( FT ) program and it ’s effect on postoperative recovery . Methods : All patients , scheduled for elective segmental colorectal resection were treated in a FT program ( FT group ) . Data were compared to a control group operated for elective colorectal resections and treated in a traditional care program ( TC group ) . Data from the FT group were collected prospect ively , data from the TC group retrospectively . Outcome parameters included the number of successfully applied FT modalities , patient satisfaction , morbidity rate , re-operation rate , primary ( PHS ) and total hospital stay ( THS ) , and readmission rate . Results : One-hundred and seven patients were included ( 55 FT group vs. 52 TC group ) . The groups were comparable for patient characteristics such as age and cr-POSSUM score ( p = 0.22 and p = 0.40 ) . An average of 7.4 of 13 predefined FT modalities were successfully achieved per patient . Patient satisfaction was comparable ( p = 0.84 ) . Seven versus 5 patients required a re-operation in the FT and TC groups , respectively ( p = 0.52 ) . Morbidity rate was comparable ( n = 16 vs. 15 , p = 0.83 ) . Median PHS was 4.0 vs. 6.0 days and median THS was 4.0 vs. 6.5 days in the FT and TC groups ( p < 0.01 and p < 0.03 , respectively ) . Six vs. 3 patients were re-admitted in the FT and TC groups , respectively ( p = 0.49 ) . Conclusion : Implementation of all FT modalities was difficult since a rather low number of pre-defined FT modalities was effectively realized . Despite incomplete implementation , PHS and THS were shorter in the FT group without affecting patient satisfaction Multimodal optimization of surgical care has been associated with reduced hospital stay and improved physical function . The aim of this r and omized trial was to compare multimodal optimization with st and ard care in patients undergoing colonic resection OBJECTIVE To investigate the feasibility of a 48-hour postoperative stay program after colonic resection . SUMMARY BACKGROUND DATA Postoperative hospital stay after colonic resection is usually 6 to 12 days , with a complication rate of 10 % to 20 % . Limiting factors for early recovery include stress-induced organ dysfunction , paralytic ileus , pain , and fatigue . It has been hypothesized that an accelerated multimodal rehabilitation program with optimal pain relief , stress reduction with regional anesthesia , early enteral nutrition , and early mobilization may enhance recovery and reduce the complication rate . METHODS Sixty consecutive patients undergoing elective colonic resection were prospect ively studied using a well-defined postoperative care program including continuous thoracic epidural analgesia and enforced early mobilization and enteral nutrition , and a planned 48-hour postoperative hospital stay . Postoperative follow-up was scheduled at 8 and 30 days . RESULTS Median age was 74 years , with 20 patients in ASA group III-IV . Normal gastrointestinal function ( defecation ) occurred within 48 hours in 57 patients , and the median hospital stay was 2 days , with 32 patients staying 2 days after surgery . There were no cardiopulmonary complications . The readmission rate was 15 % , including two patients with anastomotic dehiscence ( one treated conservatively , one with colostomy ) ; other readmissions required only short-term observation . CONCLUSION A multimodal rehabilitation program may significantly reduce the postoperative hospital stay in high-risk patients undergoing colonic resection . Such a program may also reduce postoperative ileus and cardiopulmonary complications . These results may have important implication s for the care of patients after colonic surgery and in the future assessment of open versus laparoscopic colonic resection INTRODUCTION Laparoscopic ( LAP ) versus open ( CON ) colonic resection with traditional perioperative care has some short term benefits postoperatively regarding functional recovery . Whether these benefits may also occur when all patients are treated with multimodal " fast-track"-rehabilitation programs is question able . METHODS Patients undergoing elective left sided colonic surgery were prospect ively non r and omised observed . The " fast-track " program included patient information , thoracic peridural analgesia , forced mobilisation and oral intake , and stress reduction . Endpoints were duration of postoperative ileus and hospital stay , general- and local complication , and pulmonary function . RESULTS 147 consecutive patients were operated on , 47 open and 100 laparoscopically . The time until oral intake was completed seemed to be shorter in the LAP-group ( p=0.07 ) followed by a shorter hospital stay ( p<0.01 ) . The pulmonary function was postoperatively improved in the LAP-group compared to the CON-group ( p<0,01 ) . General complications ( LAP 9 % vs. CON 17 % ) were non significantly increased in the CON-group . Local complications increased in the CON-group ( LAP 13 % vs. CON 28 % , p<0,05 ) . CONCLUSION Even with perioperative " fast-track"-rehabilitation programs short term advantages were found in laparoscopic compared with open colonic surgery in a non r and omised population . The clinical relevance should be examined in controlled r and omised trials Abstract INTRODUCTION : In an era of dwindling hospital re sources and increasing medical costs , safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare re sources . Although several protocol s have been reported to reduce postoperative stay , no Level I evidence exists for their use in routine clinical practice . METHODS : Sixty-four patients undergoing laparotomy and intestinal or rectal resection were r and omly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care . Time to discharge from hospital , complication and readmission rates , pain level , quality of life , and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery . Subgroups were defined to evaluate those who derived the optimal benefit from the protocol . RESULTS : Pathway patients spent less total time in the hospital after surgery ( 5.4 vs. 7.1 days ; P = 0.02 ) and less time in the hospital during the primary admission than traditional patients . Patients younger than 70 years old had greater benefits than the overall study group ( 5 vs. 7.1 days ; P = 0.01 ) . Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway ( P = 0.01 ) . There was no difference between pathway and traditional patients for readmission or complication rates , pain score , quality of life after surgery , or overall satisfaction with the hospital stay . CONCLUSIONS : Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet . Pathway patients have a shorter hospital stay , with no adverse effect on patient satisfaction , pain scores , or complication rates . Patients younger than 70 years of age derive the optimal benefit , and increased surgeon experience improves outcome BACKGROUND Multimodal postoperative care regimens accelerate recovery after abdominal surgery . The benefit of thoracic epidural ( TE ) analgesia over patient-controlled analgesia ( PCA ) remains unproven when used with a fast-track postoperative care plan . METHODS Fifty-six patients undergoing major intestinal resection , and on a fast-track postoperative care plan , were r and omized to preemptive TE or PCA . Patients were evaluated at st and ard time points for pain score , quality of life ( Short Form-36 ) , and complications . Oral analgesia was substituted for TE and PCA on the second postoperative day . Discharge criteria were identical for both groups . RESULTS Six patients ( 20.6 % ) had a failed epidural . There was no difference in length of stay ( 5.8 versus 6.2 days , TE versus PCA , P = .55 ) , total length of stay ( including readmissions ) , pain scores , quality of life , complications , or hospital costs at any time point . CONCLUSION TE offers no advantage over PCA for patients undergoing major intestinal resections who are on a fast-track postoperative care plan using PCA Objective The primary endpoint was to compare the impact of laparoscopic and open colorectal surgery on 30-day postoperative morbidity . Lymphocyte proliferation to mitogens and gut oxygen tension were surrogate endpoints . Summary Background Data Evidence -based proof of the effect of laparoscopic colorectal surgery on immunometabolic response and clinical ly relevant outcome variables is scanty . Further r and omized trials are desirable before proposing laparoscopy as a superior technique . Methods Two hundred sixty-nine patients with colorectal disease were r and omly assigned to laparoscopic ( n = 136 ) or open ( n = 133 ) colorectal resection . Four trained members of the surgical staff who were not involved in the study registered postoperative complications . Lymphocyte proliferation to C and ida albicans and phytohemagglutinin was evaluated before and 3 and 15 days after surgery . Operative gut oxygen tension was monitored continuously by a polarographic microprobe . Results In the laparoscopic group the conversion rate was 5.1 % . The overall morbidity rate was 20.6 % in the laparoscopic group and 38.3 % in the open group . Postoperative infections occurred in 15 of the 136 patients in the laparoscopic group and 31 of the 133 patients in the open group . The mean length of hospital stay was 10.4 ± 2.9 days in the laparoscopic group and 12.5 ± 4.1 days in the open group . On postoperative day 3 , lymphocyte proliferation was impaired in both groups . Fifteen days after surgery , the proliferation index returned to baseline values only in the laparoscopic group . Intraoperative gut oxygen tension was higher in the laparoscopic than in the open group . Conclusions Laparoscopic colorectal surgery result ed in a significant reduction of 30-day postoperative morbidity . Lymphocyte proliferation and gut oxygen tension were better preserved in the laparoscopic group than in the open group OBJECTIVE In elective large bowel surgery the incidence of general complications with st and ard perioperative care is up to 27 % . Hospital discharge occurs 10 to 15 days after a conventional or laparoscopic colonic resection . The aim of a fast track management is to reduce the number of general complications and the length of hospital stay . MATERIAL AND METHODS We prospect ively evaluated a multimodal protocol in our service utilizing a combined thoracic epidural analgesia , an early mobilization and oral nutrition to accelerate postoperative recovery after elective colonic surgery . RESULTS One hundred thirty-two consecutive patients aged an average of 66 years ( range 22 - 88 ) were operated by laparotomy ( n = 71 ) or laparoscopy ( n = 61 ) and treated with the fast track rehabilitation protocol . Surgical complications occurred in 15 patients ( 11 % ) , four of these had an anastomotique leakage ( 3 % ) . General complications occurred in 11 patients ( 8 % ) , the mortality was 1 % . The median length of hospital stay was four days ( range 3 - 77 ) and 14 patients ( 11 % ) had to be readmitted . CONCLUSION Application of a fast track rehabilitation protocol lowered the number of general complications and reduced the duration of hospital stay in our study There has been no r and omized clinical trial of the costs of laparoscopic colonic resection ( LCR ) compared with those of open colonic resection ( OCR ) in the treatment of colonic cancer Postoperative organ dysfunction contributes to morbidity , hospital stay and convalescence . Multimodal rehabilitation with epidural analgesia , early oral feeding , mobilization and laxative use after colonic resection has reduced ileus and hospital stay Background Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs . Both focus on a faster recovery and shorter hospital stay . The r and omized controlled multicenter LAFA-trial ( LAparoscopy and /or FAst track multimodal management versus st and ard care ) was conceived to determine whether laparoscopic surgery , fast track perioperative care or a combination of both is to be preferred over open surgery with st and ard care in patients having segmental colectomy for malignant disease . Methods / design The LAFA-trial is a double blinded , multicenter trial with a 2 × 2 balanced factorial design . Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be r and omized to either open or laparoscopic colectomy , and to either st and ard care or the fast track program . This factorial design produces four treatment groups ; open colectomy with st and ard care ( a ) , open colectomy with fast track program ( b ) , laparoscopic colectomy with st and ard care ( c ) , and laparoscopic surgery with fast track program ( d ) . Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days . Secondary outcome parameters are quality of life two and four weeks after surgery , overall hospital costs , morbidity , patient satisfaction and readmission rate . Based on a mean postoperative hospital stay of 9 + /- 2.5 days a group size of 400 patients ( 100 each arm ) can reliably detect a minimum difference of 1 day between the four arms ( alfa = 0.95 , beta = 0.8 ) . With 100 patients in each arm a difference of 10 % in subscales of the Short Form 36 ( SF-36 ) question naire and social functioning can be detected . Discussion The LAFA-trial is a r and omized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease |
461 | 22,895,984 | Minor adverse events reported included transient post-injection pain , facial redness and warmth .
AUTHORS ' CONCLUSIONS Based upon moderate evidence from five trials , our review was unable to establish any advantage in terms of pain , function , shoulder range of motion or safety , of ultrasound-guided glucocorticoid injection for shoulder disorders over either l and mark-guided or intramuscular injection .
The lack of any added benefit of ultrasound guided subacromial bursal injection over glucocorticoid injection administered into the upper gluteal muscles of the buttock suggests that the benefits of glucocorticoid may arise through systemic rather than local effects .
Therefore , although ultrasound guidance may improve the accuracy of injection to the putative site of pathology in the shoulder , it is not clear that this improves its efficacy to justify the significant added cost | BACKGROUND Traditionally , glucocorticoid injection for the treatment of shoulder pain has been performed guided by anatomical l and marks alone .
With the advent of readily available imaging tools such as ultrasound , image-guided injections have increasingly become accepted into routine care .
While there is some evidence that the use of imaging improves accuracy , it is unclear from current evidence whether or not it improves patient-relevant outcomes .
OBJECTIVES The aim of this review was to assess whether image-guided glucocorticoid injections improve patient-relevant outcomes compared to l and mark-guided or systemic intramuscular injections in patients with shoulder pain . | OBJECTIVE To determine whether arthrographic distension with a mixture of saline and steroid , in patients with painful stiff shoulder for at least 3 months , is better than placebo in improving function , pain , and range of motion at 3 , 6 , and 12 weeks . METHODS A r and omised , placebo controlled trial with participant and outcome assessor blinding in which shoulder joint distension with normal saline and corticosteroid was compared with placebo ( arthrogram ) . Outcome measures , assessed at 3 , 6 , and 12 weeks , included a shoulder-specific disability measure ( SPADI ) , a patient preference measure ( Problem Elicitation Technique ( PET ) ) , pain , and range of active motion . RESULTS From 96 potential participants , 48 were recruited . Four withdrew from the placebo group after the 3 week assessment and three subsequently received arthrographic distension with saline and steroid . At 3 weeks , significantly greater improvement in SPADI ( p = 0.005 ) , PET , overall pain , active total shoulder abduction , and h and behind back was found in participants in the joint distension and steroid group than in the placebo group . At 6 weeks the results of the intention to treat analysis favoured joint distension , although the between-group differences were only significant for improvement in PET ( difference in mean change in PET between groups = 45.9 ( 95 % CI 3.2 to 88.7 ) . Excluding the four withdrawals , the between-group differences for the disability and pain measures significantly favoured distension over placebo . At 12 weeks , both the intention to treat analysis and an analysis excluding the four withdrawals demonstrated a significantly greater improvement in PET score for the distension group . CONCLUSIONS Short term efficacy of arthrographic distension with normal saline and corticosteroid over placebo was demonstrated in patients with painful stiff shoulder OBJECTIVE To study the effect of accuracy on the clinical outcome of local steroid injections to the shoulder . METHODS 37 patients with shoulder symptoms of at least two months ’ duration received local injections of a mixture of triamcinolone and radiographic contrast material using a st and ardised technique . Radiographs of the joint were taken immediately afterwards . Details of the patients ’ symptoms ( assessed by visual analogue scales ) and range of movement at the joint were obtained before and two weeks after the injection . At follow up the patients were also assessed by means of a five point global rating scale of maximum and current benefit . RESULTS 14 of the 38 procedures ( 37 % ) were judged to be accurately placed : four of the 14 attempted subacromial injections ( 29 % ) and 10 of the 24 attempted glenohumeral injections ( 42 % ) . There were significant differences in relation to outcome between the accurately placed and the inaccurately placed groups . CONCLUSIONS Accuracy of steroid placement by injection in patients with shoulder symptoms may significantly affect the clinical outcome Background Blind injection of the subacromial-sub-deltoid bursa ( SSB ) for diagnostic purpose s ( Neer test ) or therapeutic purpose s ( corticosteroid therapy ) is frequently used . Poor response to previous blind injection or side effects may be due to a misplaced injection . It is assumed that ultrasound (US)-guided injections are more accurate than blind injections . In a r and omized study , we compared the accuracy of blind injection to that of US-guided injection into the SSB . Patients and methods 20 consecutive patients with impingement syndrome of the shoulder were r and omized for blind or US-guided injection in the SSB . Injection was performed either by an experienced orthopedic surgeon or by an experienced musculoskeletal radiologist . A mixture of 1 m’L methylprednisolone acetate , 4 mL prilocaine hydrochloride and 0.02 mL ( 0.01 mmol ) Gadolinium DTPA was injected . Immediately after injection , a 3D-gradient T1-weighted magnetic resonance scan of the shoulder was performed . The location of the injected fluid was independently assessed by 2 radiologists who were blinded as to the injection technique used . Results The accuracy of blind and US-guided injection was the same . The fluid was injected into the bursa in all cases . Interpretation Blind injection into the SSB is as reliable as US-guided injection and could therefore be used in daily routine . US-guided injections may offer a useful alternative in difficult cases , such as with changed anatomy postoperatively or when there is no effective clinical outcome The histological changes found in the supraspinatus tendon have similarities with the findings in Achilles- , patellar- and extensor carpi radialis brevis (ECRB)-tendinopathy . In recent studies , we have found a vasculo-neural ingrowth in chronic painful Achilles and patellar tendinopathy , and demonstrated good short-term clinical effects with injections of the sclerosing substance polidocanol . In this collaborative two-centre pilot study , 15 patients ( 10 males and 5 females , mean age 46 years ) with a long duration of shoulder pain ( mean 28 months ) , and given the diagnosis chronic painful shoulder impingement syndrome , were included . They had tried rest , traditional rehabilitation exercises and multiple subacromial corticosteroid injections , without effect . We found vascularity ( neovessels ) in chronic painful , but not in pain-free , supraspinatus tendons , and prospect ively studied the clinical effects of ultrasound ( US ) and colour Doppler (CD)-guided injections of polidocanol , targeting the area with neovessels . The patients evaluated the amount of shoulder pain during horizontal shoulder activity on a visual analogue scale ( VAS ) , and satisfaction with treatment . Two ( median ) ( range 1–5 ) polidocanol treatments ( with 4–8 weeks in between ) were given . In four patients ( considered treatment failure ) , cortisone was injected into an inflamed subacromial bursa at one separate occasion weeks after the last polidocanol injection . At follow-up , 8 ( median ) ( range 4–17 ) months after the treatment , 14 patients were satisfied with the result . Using the visual analogue scale evaluation ( VAS ) , the pain dropped from 79 before treatment to 21 at follow-up ( P < 0.05 ) . In the short-term perspective , sclerosing polidocanol injections targeting the neovessels in the supraspinatus tendon and /or bursa wall seems to have a potential to reduce the pain during shoulder loading activity Background Hydrodilatation of the glenohumeral joint is by several authors reported to improve shoulder pain and range of motion for patients with adhesive capsulitis . Procedures described often involve the injection of corticosteroids , to which the reported treatment effects may be attributed . Any important contribution arising from the hydrodilatation procedure itself remains to be demonstrated . Methods In this r and omized trial , a hydrodilatation procedure including corticosteroids was compared with the injection of corticosteroids without dilatation . Patients were given three injections with two-week intervals , and all injections were given under fluoroscopic guidance . Outcome measures were the Shoulder Pain and Disability Index ( SPADI ) and measures of active and passive range of motion . Seventy-six patients were included and groups were compared six weeks after treatment . The study was design ed as an open trial . Results The groups showed a rather similar degree of improvement from baseline . According to a multiple regression analysis , the effect of dilatation was a mean improvement of 3 points ( confidence interval : -5 to 11 ) on the SPADI 0–100 scale . T-tests did not demonstrate any significant between-group differences in range of motion . Conclusion This study did not identify any important treatment effects result ing from three hydrodilatations that included steroid compared with three steroid injections alone . Trial registration The study is registered in Current Controlled Trials with the registration number IS RCT N90567697 PURPOSE The study goal was to examine the targeting accuracy of subacromial injection to the shoulder and the influence of the location of the injected structure . TYPE OF STUDY A prospect i ve nonr and omized study . METHODS Fifty-three patients ( 56 shoulders ; 34 women and 19 men ; mean age , 74.5 years ; range , 49 to 91 ) with impingement signs ( Neer , Hawkins ) of at least 2 months ' duration received a subacromial injection of a mixture of 0.5 mL ( 2.5 mg ) betamethasone acetate and 3 mL of radiographic contrast material ( iotrolan ) and 7 mL of 1 % lidocaine using a lateral approach . Radiographs of the shoulder joint were taken immediately after the injection to determine the structure reached by the injection . Details of pain expressed as Neer and Hawkins impingement signs were obtained before and 15 minutes after the injection , and subjectively assessed using a 4-point self-administered pain score . Pain reduction result ing from subacromial and intradeltoid injection was compared . RESULTS Thirty-nine of the 56 injections ( 70 % ) were judged to have reached the subacromial bursa . Twelve ( 21 % ) were seen to have entered the deltoid muscle ; 2 ( 4 % ) were in the glenohumeral joint ; and 3 ( 5 % ) were subcutaneous . A comparison of subacromial bursal with intradeltoid injection showed no significant differences in pain reduction expressed as impingement signs ( 1.5 vs 1.7 in the Neer impingement sign and 1.6 vs 1.6 in the Hawkins impingement sign , respectively ) . CONCLUSIONS This study showed that subacromial injection was a relatively difficult procedure . A high incidence of injections that missed the subacromial bursa would be a sufficient reason to refrain from repeated usage of corticosteroids . These results also suggest that pain relief could be attained whether the injected material reached the subacromial bursa or the deltoid muscle . Successful pain relief after intradeltoid injection seems to call into question the diagnostic value of a positive Neer impingement test Twenty-six patients with frozen shoulder syndrome ( Stage 2 and 3 ) were included in this study conducted at Dr. Kariadi General Hospital , Semarang , Indonesia and r and omly allocated into 2 groups : 40 mg triamcinolone intra-articular injection and triamcinolone oral tablets . The result showed that triamcinolone intra-articular injection group " cured " rate was 5.8 times higher at week one compared to the triamcinolone tablet group . Sixty-two percent of the cases with triamcinolone intra-articular injection achieved their " cured " condition after one week of therapy , compared with only 14 % of the triamcinolone tablets group . We conclude that , intra-articular corticosteroid injection provide faster improvement compared to oral route Objective To compare the effectiveness of ultrasound guided corticosteroid injection in the subacromial bursa with systemic corticosteroid injection in patients with rotator cuff disease . Design Double blind r and omised clinical trial . Setting Outpatient clinic of a physical medicine and rehabilitation department in Oslo , Norway . Patients 106 patients with rotator cuff disease lasting at least three months . Interventions Ultrasound guided corticosteroid and lidocaine injection in the subacromial bursa and lidocaine injection in the gluteal region ( local group ) ; corticosteroid and lidocaine injection in the gluteal region and ultrasound guided lidocaine injection in the subacromial bursa ( systemic group ) . Main outcome measures Difference in improvement in the overall shoulder pain and disability index score after six weeks . Results Six weeks after the intervention , the mean difference in improvement in overall shoulder pain and disability index score between the local group and the systemic group was −5.2 ( 95 % confidence interval −13.9 to 3.5 ) ; it was −4.1 ( −12.3 to 4.1 , P=0.32 ) after adjustment for baseline score . A small but statistically significant difference in improvement between groups occurred in favour of the local group for two secondary outcome measures : the Western Ontario rotator cuff index ( 8.1 , 0.7 to 15.6 ) and change in main complaint ( 2.0 , 0 to 4 ) . Conclusions No important differences in short term outcomes were found between local ultrasound guided corticosteroid injection and systemic corticosteroid injection in rotator cuff disease . Trial registration Clinical trials NCT00640575 Objective To determine whether fluoroscopic guidance improves outcomes of injections for greater trochanteric pain syndrome . Design Multicentre double blind r and omised controlled study . Setting Three academic and military treatment facilities in the United States and Germany . Participants 65 patients with a clinical diagnosis of greater trochanteric pain syndrome . Interventions Injections of corticosteroid and local anaesthetic into the trochanteric bursa , using fluoroscopy ( n=32 ) or l and marks ( that is , “ blind ” injections ; n=33 ) for guidance . Main outcome measures Primary outcome measures : 0 - 10 numerical rating scale pain scores at rest and with activity at one month ( positive categorical outcome predefined as ≥50 % pain reduction either at rest or with activity , coupled with positive global perceived effect ) . Secondary outcome measures included Oswestry disability scores , SF-36 scores , reduction in drug use , and patients ’ satisfaction . Results No differences in outcomes occurred favouring either the fluoroscopy or blind treatment groups . One month after injection the average pain scores were 2.7 at rest and 5.0 with activity in the fluoroscopy group compared with 2.2 and 4.0 in the blind injection group . Three months after the injection , 15 ( 47 % ) patients in the blind group and 13 ( 41 % ) in the fluoroscopy group continued to have a positive outcome . Conclusion Although using fluoroscopic guidance dramatically increases treatment costs for greater trochanteric pain syndrome , it does not necessarily improve outcomes . Trial registration Clinical trials Corticosteroids are commonly used in the treatment of the impingement syndrome . Efficacy , as well as accurate placement , have been question ed . The purpose of this prospect i ve , r and omized study is to assess the accuracy of subacromial injections and to correlate accuracy with short term clinical outcome at 3 months . Sixty shoulders , which were diagnosed with impingement syndrome , were r and omized to receive a subacromial injection of corticosteroids , local anesthetic , and contrast dye from 1 of 3 locations : anterolateral , lateral , or posterior . Accuracy was confirmed by 3 radiographic views of the shoulder , while clinical ratings were assessed by the UCLA shoulder score and a 10-point visual pain analog scale during the initial , post-injection , and 3-month visits . The overall accuracy was 70 % , with no difference among the 3 portals . Accuracy was not related to body mass index . Furthermore , accurate injections did not significantly improve the UCLA score , pain scale , or patient satisfaction at 3 months . In contrast , accurate injections produced a positive Neer 's impingement test more often ( 35/39 vs 9/16 ; P = .009 ) . Overall , there was an improvement in the UCLA score ( 26.2 - 32.2 ; P < .001 ) and a decrease in the pain scale ( 7.2 - 3.43 ; P < .001 ) at 3-month follow-up . In conclusion , the accuracy of injection was 70 % . Clinical improvement did not correlate with accuracy ; however , accuracy did reliably produce a positive impingement test . This multimodal treatment plan did produce significant improvement in shoulder function and pain level in the short term OBJECTIVE To compare ultrasonography with bone scintigraphy in the diagnosis of plantar fasciitis and to compare ultrasound-guided injection with palpation-guided injection in the management of idiopathic plantar fasciitis . METHODS Twenty-three patients with a clinical diagnosis of idiopathic plantar fasciitis in 28 heels underwent ultrasonography and bone scintigraphy of both heels at baseline . The patients were r and omized to ultrasound- or palpation-guided injection of triamcinolone hexacetonide and xylocaine into the plantar fascia . The 100 mm visual analogue scale ( VAS ) of pain , the heel tenderness index ( HTI ) , and ultrasonography were performed at baseline and follow-up ( mean=13.4 weeks ) . RESULTS The mean thickness ( + /-st and ard error of the mean ) of the plantar fascia , measured by ultrasonography , was 5.7+/-0.3 mm in symptomatic heels as compared with 3.8+/-0.2 mm in asymptomatic heels ( P<0.001 ) . Ultrasonography findings correlated with bone scintigraphic findings in the diagnosis of plantar fasciitis ( P<0.001 ) . Fourteen heels were r and omized to ultrasound-guided injection , 10 heels were r and omized to palpation-guided injection and four heels were not injected . Ultrasound- and palpation-guided injection result ed in significant mean improvements in VAS [ 39.6+/-9.2 ( ultrasound ) vs 41.5+/-8 ( palpation ) ] and HTI [ 1.35+/-0.2 ( ultrasound ) vs 1.3+/-0.4 ( palpation ) ] . There was no significant difference in the response rate following corticosteroid injection by either modality ( ultrasound=13/14 , palpation=8/10 ) . Following injection , the mean thickness of the plantar fascia decreased from 5.7+/-0.3 mm to 4.65+/-0.4 mm ( P<0.01 ) . CONCLUSION Ultrasonography and bone scintigraphy are equally effective in the diagnosis of plantar fasciitis . Ultrasound-guided injection is effective in the management of plantar fasciitis but is not more effective than palpation-guided injection . Ultrasonography may be used as an objective measure of response to treatment in plantar fasciitis Aim To compare the effectiveness of l and mark-guided local injections and ultrasonography ( USG ) guided injections for shoulder pain . Methods A total 60 consecutive patients with shoulder pain due to soft tissue disorders was enrolled , and r and omly assigned to receive triamcinolone ( 40 mg ) either by l and mark-guided ( LMG , n=30 ) or USG guided ( n=30 ) injection . The patients were evaluated on admission and 6 weeks after the injection . Clinical assessment included demographic and clinical data , a visual analoge scale ( VAS ) for pain ( 0 to 10 cm ) , the Constant scale ( 0 to 100 ) for function , passive and active shoulder range of motion ( ROM ) with goniometric evaluation , and postinjection adverse effects . Results Initial demographic , clinical and USG findings in the groups exhibited no significant differences . Six weeks after injection , the VAS and the Constant score showed a significantly better improvement in USG group compared with LMG group ( mean VAS score decrease : 4.0±1.7 for USG vs. 2.2±0.9 for LMG , P<0.05 ; mean Constant score change : 32.2 for USG vs. 12.2 for LMG , P<0.05 ) . Significant improvements were observed in active and passive ROM values in both groups , USG group values being better . Initially 18 patients in LMG and 24 patients in USG had limited shoulder ROM , of which 6 was returned to normal values in LMG group and 12 in USG group at 6 week after injection ( P<0.05 ) . Conclusions Our results indicate that the injection of corticosteroids to patients with shoulder pain due to soft tissue disorders under the USG-guidance may improve therapeutic effectiveness and reduce adverse effects Chen MJL , Lew HL , Hsu TC , Tsai WC , Lin WC , Tang SFT , Lee YC , Hsu RCH , Chen CPC : Ultrasound-guided shoulder injections in the treatment of subacromial bursitis . Am J Phys Med Rehabil 2006;85:31–35 . Objective : To investigate the treatment effectiveness between ultrasound-guided and blind injection techniques in the treatment of subacromial bursitis . Design : A total of 40 patients with sonographic confirmation of subacromial bursitis were recruited into this study . These patients were divided into blind and ultrasound-guided injection groups . The shoulder abduction range of motion was compared before injections and 1 wk after the completion of injections in both groups . Results : The shoulder abduction range of motion before injection in the blind injection group was 71.03 ± 12.38 degrees and improved to 100 ± 18.18 degrees 1 wk after the injection treatments . However , the improvement did not reveal significant statistical differences ( P > 0.05 ) . The shoulder abduction range of motion before injection in the ultrasound-guided injection group was 69.05 ± 14.72 degrees and improved to 139.29 ± 20.14 degrees 1 wk after the injection treatments ( P < 0.05 ) . Conclusions : Ultrasound may be used as an adjuvant tool in guiding the needle accurately into the inflamed subacromial bursa . The ultrasound-guided injection technique can result in significant improvement in shoulder abduction range of motion as compared with the blind injection technique in treating patients with subacromial bursitis Ninety-five patients with 107 trigger digits were divided into 2 groups and studied prospect ively to evaluate steroid injection placement and efficacy . In 1 group , an attempt was made to deliver 1 injection into the tendon sheath at the A1 pulley . In the other group , 1 injection infiltrated the subcutaneous tissues overlying the A1 pulley . Radiopaque dye provided contrast to the injection medium , and postinjection x-rays identified the true delivery site of the steroid solution . Of the 52 digits into which intrasheath injection was attempted , 19 digits ( 37 % ) received all the injection within the sheath , 24 ( 46 % ) received medication into both the sheath and the subcutaneous tissues , and 9 ( 17 % ) received no medication within the tendon sheath . The results were analyzed to determine whether injection placement influences the efficacy of steroid injection . The confirmed all-sheath injection group exhibited a 47 % good response , the mixed sheath and subcutaneous group had a 50 % good response , and the all-subcutaneous group had a 70 % good response . The results of this study suggest that true intrasheath injection offers no apparent advantage over subcutaneous injection in the treatment of trigger digits PURPOSE To assess the accuracy of shoulder infiltrations in the subacromial bursa ( SAB ) by a posterior or an anteromedial approach . Magnetic resonance imaging ( MRI ) and clinical outcome were used for evaluation . TYPE OF STUDY A prospect i ve r and omized study . METHODS Thirty-three patients ( 22 women , 11 men ; average age , 46 years ; range , 25 to 64 years ) with clinical signs of subacromial impingement were infiltrated with a mixture of bupivacaine , methylprednisolone , and gadolinium-DTPA directly followed by MRI to determine the actual site of injection . The SAB was r and omly infiltrated posteriorly ( n = 17 ) or anteromedially ( n = 16 ) . Injection confidence of the surgeon and body-mass index of the patient were recorded . Follow-up consisted of the Constant Score , Simple Shoulder Test , and visual analog scale score for pain taken within 24 hours and 6 weeks after infiltration . RESULTS Thirteen injections ( 76 % ) were in the SAB with a posterior approach and 10 ( 69 % ) with an anteromedial approach . Many surrounding structures were hit as well , especially the rotator cuff . A positive correlation between the injection confidence of the orthopaedic surgeon and the MRI was found in 66 % . Only injection of the SAB alone result ed in a significant decrease of the pain ( P = .004 ) and an increase in the functional scores . Injection in the bursa and rotator cuff muscle showed a significant increase in pain ( P = .032 ) but no change in clinical scores . The body mass index had no influence on the scores . CONCLUSIONS Injections in the SAB are inaccurate , despite the confident feeling of the clinician . The finding that many different structures can be infiltrated with 1 injection can create both false-positive and -negative results . LEVEL OF EVIDENCE Level II BACKGROUND Suprascapular nerve block is a safe and effective treatment for chronic shoulder pain in arthritis , which can be performed either by direct imaging ( CT guided ) or in the clinic using anatomical l and marks to determine needle placement . OBJECTIVE To compare a CT guided versus an anatomical l and mark approach in a r and omised , single blind trial examining the efficacy of suprascapular nerve block for shoulder pain in patients with degenerative joint/rotator cuff disease . METHODS 67 patients with chronic shoulder pain from degenerative disease participated in the trial . 77 shoulders were r and omised . The group r and omised to receive the block through the anatomical l and mark approach received a single suprascapular nerve block . Those in the CT guided group received an injection of methylprednisolone acetate and a smaller volume of bupivacaine around the suprascapular nerve . The patients were followed up for 12 weeks by a " blinded " observer and review ed at weeks 1 , 4 , and 12 after the injection . RESULTS Significant improvements were seen in all pain scores and disability in the shoulders receiving both types of nerve block , with no significant differences in the improvement in pain and disability between the two approaches at any time . Improvements in pain and disability scores were clinical ly and statistically significant . No significant adverse effects occurred in either group . Patient satisfaction scores for pain relief using either approach were high . CONCLUSION The CT guided control and l and mark approaches to performing suprascapular nerve blocks result in similar significant and prolonged pain and disability reductions ; both approaches are safe Objective . This r and omized controlled study addressed whether sonographic needle guidance affected clinical outcomes of intraarticular ( IA ) joint injections . Methods . In total , 148 painful joints were r and omized to IA triamcinolone acetonide injection by conventional palpation-guided anatomic injection or sonographic image-guided injection enhanced with a one-h and ed control syringe ( the reciprocating device ) . A one-needle , 2-syringe technique was used , where the first syringe was used to introduce the needle , aspirate any effusion , and anesthetize and dilate the IA space with lidocaine . After IA placement and synovial space dilation were confirmed , a syringe exchange was performed , and corticosteroid was injected with the second syringe through the indwelling IA needle . Baseline pain , procedural pain , pain at outcome ( 2 weeks ) , and changes in pain scores were measured with a 0–10 cm visual analog pain scale ( VAS ) . Results . Relative to conventional palpation-guided methods , sonographic guidance result ed in 43.0 % reduction in procedural pain ( p < 0.001 ) , 58.5 % reduction in absolute pain scores at the 2 week outcome ( p < 0.001 ) , 75 % reduction in significant pain ( VAS pain score ≥ 5 cm ; p < 0.001 ) , 25.6 % increase in the responder rate ( reduction in VAS score ≥ 50 % from baseline ; p < 0.01 ) , and 62.0 % reduction in the nonresponder rate ( reduction in VAS score < 50 % from baseline ; p < 0.01 ) . Sonography also increased detection of effusion by 200 % and volume of aspirated fluid by 337 % . Conclusion . Sonographic needle guidance significantly improves the performance and outcomes of outpatient IA injections in a clinical ly significant manner OBJECTIVE Local corticosteroid injections , commonly accepted by rheumatologists to be effective treating painful shoulder , have shown controversial results . High frequency ultrasonography is an accurate and safe imaging modality for guiding musculoskeletal injections . We prospect ively compared the short term response to r and omized blind injection versus sonographic-guided injection of local corticosteroid in patients with painful shoulder . METHODS We studied 41 consecutive patients with painful shoulder . Patients with previous trauma or chronic inflammatory arthritis were excluded . No patient had received previous physiotherapy or local steroid injection in the shoulder . Patients were r and omized to receive either a blind subacromial injection of 20 mg triamcinolone ( Group 1 , n = 20 ) or a sonographic guided injection of 20 mg triamcinolone ( Group 2 , n = 21 ) by the same rheumatologist blinded to the clinical evaluation . In both groups we recorded shoulder abnormalities and the location of the steroid postinjection by ultrasound . Each patient was clinical ly assessed within 5 days before injection and 6 weeks after injection by another rheumatologist without knowledge of the injection technique performed . Clinical assessment included demographic and clinical data , a visual analog scale ( VAS ) for pain ( 0 - 100 ) , the Shoulder Function Assessment ( SFA ) scale ( 0 - 70 ) , and postinjection adverse effects . No patient received physical therapy during the followup period . Initially , demographic , clinical , and ultrasonographic findings in both groups showed no significant differences . RESULTS Six weeks after injection , the VAS and the SFA score showed a significantly greater improvement in Group 2 compared with Group 1 ( mean VAS score change 34.9 for Group 2 vs 7.1 for Group 1 , p < 0.001 ; and mean SFA score change 15 for Group 2 vs 5.6 for Group 1 , p = 0.012 ) . One patient in Group 1 reported mild postinjection adverse effects . CONCLUSION We suggest that sonographic-guided corticosteroid injections should be indicated , at least , in patients with poor response to previous blind injection to ensure accurate medication placement in order to improve therapeutic effectiveness UNLABELLED Lee H-J , Lim K-B , Kim D-Y , Lee K-T. R and omized controlled trial for efficacy of intra-articular injection for adhesive capsulitis : ultrasonography-guided versus blind technique . OBJECTIVE To evaluate the clinical effect of ultrasonography (US)-guided intra-articular injections compared with a blind ( unguided ) technique for the treatment of adhesive capsulitis . DESIGN R and omized controlled trial . SETTING Outpatient rehabilitation clinic . PARTICIPANTS Patients ( N=43 ) diagnosed as having adhesive capsulitis after clinical examinations and radiologic and ultrasonographic study . INTERVENTION Under either US-guided or a blind technique , patients received a 20-mg intra-articular injection of triamcinolone mixed with 1.5mL 2 % lidocaine and 4mL normal saline in the first week followed by 5 weekly injections of sodium hyaluronate . MAIN OUTCOME MEASURES A visual analog scale for pain intensity , range of motion ( ROM ) of the shoulder ( flexion , abduction , external rotation , and internal rotation ) , and general shoulder function during daily activities at preinjection as a baseline and then every week after injection for 6 weeks for each patient . RESULTS Twenty patients out of 22 in the blind injection group and 20 out of 21 in the US-guided group finished the entire 6-week study period . The improvement in pain intensity , ROM , and shoulder function score was significantly greater in the US-guided injection group than in the blind injection group by the second week postinjection ( P<.05 ) . However , there were no further significant differences in the improvement between the 2 groups beyond the third week . CONCLUSIONS US-guided intra-articular injections may offer advantages over a blind technique for the treatment of adhesive capsulitis and may deliver clinical benefits during the first few weeks of treatment . This finding suggests that the improved targeting to the intra-articular space by using US can result in better treatment of adhesive capsulitis The author reports the results of a placebo controlled trial of Celestone Chronodose ® in the treatment of supraspinatus tendinitis involving a total of 180 patients . The results after local injection and deep gluteal injection are also compared |
462 | 17,636,774 | Treatment response appeared to vary between patient subgroups , although there was no significant difference in improvement in erectile function according to mean group age , type of relationship , and severity of ED .
There was evidence that group psychotherapy may improve erectile function .
Treatment response varied between patient subgroups , but focused sex-group therapy showed greater efficacy than control group ( no treatment ) .
In a meta- analysis that compared group therapy plus sildenafil citrate versus sildenafil , men r and omised to receive group therapy plus sildenafil showed significant improvement of successful intercourse , and were less likely than those receiving only sildenafil to drop out .
Group psychotherapy also significantly improved ED compared to sildenafil citrate alone .
Regarding the effectiveness of psychosocial interventions for the treatment of ED compared to local injection , vacuum devices and other psychosocial techniques , no differences were found | BACKGROUND Normal sexual function is a biopsychosocial process and relies on the coordination of psychological , endocrine , vascular , and neurological factors .
Recent data show that psychological factors are involved in a substantial number of cases of erectile dysfunction ( ED ) alone or in combination with organic causes .
However , in contrast to the advances in somatic research of erectile dysfunction , scientific literature shows contradictory reports on the results of psychotherapy for the treatment of ED .
OBJECTIVES To evaluate the effectiveness of psychosocial interventions for the treatment of ED compared to oral drugs , local injection , vacuum devices and other psychosocial interventions , that may include any psycho-educative methods and psychotherapy , or both , of any kind . | We provide current , normative data on the prevalence of impotence , and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study . The Massachusetts Male Aging Study was a community based , r and om sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston , Massachusetts . Blood sample s , physiological measures , socio-demographic variables , psychological indexes , and information on health status , medications , smoking and lifestyle were collected by trained interviewers in the subject 's home . A self-administered sexual activity question naire was used to characterize erectile potency . The combined prevalence of minimal , moderate and complete impotence was 52 % . The prevalence of complete impotence tripled from 5 to 15 % between subject ages 40 and 70 years . Subject age was the variable most strongly associated with impotence . After adjustment for age , a higher probability of impotence was directly correlated with heart disease , hypertension , diabetes , associated medications , and indexes of anger and depression , and inversely correlated with serum dehydroepi and rosterone , high density lipoprotein cholesterol and an index of dominant personality . Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension . We conclude that impotence is a major health concern in light of the high prevalence , is strongly associated with age , has multiple determinants , including some risk factors for vascular disease , and may be due partly to modifiable para-aging phenomena We investigated the effect of adding a psychoeducational intervention to oral sildenafil ( PsychoedPlusMed ) in the treatment of erectile dysfunction ( ED ) . Overall treatment satisfaction , as measured by the Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ; Althof & Seftel , 1995 ) , was significantly higher in the PsychoedPlusMed patients than in the sildenafil-only patients at 12 weeks and at 24 weeks . PsychoedPlusMed participants reported higher satisfaction with treatment onset , treatment duration , and sexual confidence . PsychoePlusMed participants also reported an increase in communication about sex with their partner . A brief psychoeducational intervention can improve treatment satisfaction with sildenafil therapy for ED This study compared the effectiveness of two components , a ban on sexual intercourse and communication of sexual preferences , in the treatment of couples in which the male was experiencing erectile dysfunction . Sixteen couples were r and omly assigned to one of two treatment conditions . In one condition spouses were asked to refrain from intercourse and to make an effort to communicate sexual tastes and preferences during noncoital erotic interaction . Couples in the second condition were assigned only the communication portion of the therapeutic instructions given to the first group . The treatment consisted of written instructions concerning tasks to be carried out at home . Therapist contact was minimal . Following a 1-month baseline period of self-monitoring using a daily record-keeping form , couples underwent a 1-month treatment period and follow-up testing after another month . Male subjects also underwent an endocrinological examination to ascertain testosterone and related hormone levels prior to participating in the treatment . Both treatment groups reported significant improvement in several measures of erectile functioning , general sexual functioning , and marital adjustment . However , the ban on intercourse did not add to the effectiveness of encouraging sexual communication , indicating that the former component probably did not contribute to change . Two pretreatment measures , the Sexual Interaction Inventory and testosterone level , were found to predict treatment outcome with sufficient accuracy to permit selection of future patients who might benefit from this type of treatment format . The effectiveness of a treatment consisting of written instructions with minimal therapist contact for males with erectile dysfunction have important cost-benefit implication The treatment for psychogenic erectile dysfunction has been previously managed by non-medical methods consisting of counseling with a psychiatrist , psychologist or sex therapist . The success rate for treatment with counseling has not been uniformly successful . This paper compares the treatment of psychogenic erectile dysfunction using st and ard sex therapy and self-injection therapy using low-dose PGE1 . Fifty men with psychogenic impotence were divided into two groups : st and ard sex therapy for twelve weeks or treatment using low-dose ( 2.5–5.0 μg ) of PGE1 . The results showed that men treated with low-dose PGE1 had a 47 % improvement of obtaining an unaided erection compared to 58 % improvement rate with sex therapy . 69 % of patients in the PGE1 group were satisfied with their treatment compared to 75 % receiving sex therapy . The frequency of intercourse reported in patient diaries for the two groups was similar ( 20.5 per month for PGE1 vs 20.0 per month for sex therapy . The reported duration of erection by patients receiving PGE1 therapy was longer than that reported by those receiving sex therapy ( 35 min vs 10 min ) . The comparison of the cost of treatment of the two treatment groups reveals that the sex therapy is approximately 25 % more expensive than the PGE1 treatment . This pilot study demonstrates that the efficacy of PGE1 was numerically , though not statistically , less than sex therapy in the treatment of psychogenic impotence . The cost per positive outcome with PGE1 treatment is lower than that of sex therapy treatment making PGE1 more cost-effective Abstract In a prospect i ve investigation of the long-term outcome of 140 couples who had entered sex therapy 1–6 yrs earlier for a variety of sexual dysfunctions , successful follow-up , mostly by interview , was possible with at least one partner in 75 % of cases . While recurrence of sexual difficulties was common , coping strategies were identified which often helped overcome relapses . Improvements in couples ' general relationships result ing from treatment were usually sustained . Long-term outcome was excellent for vaginismus , good for erectile dysfunction , but often poor for premature ejaculation , and especially , for female impaired sexual interest . While the results of this study support the continued use of sex therapy for sexual dysfunction , they also emphasize the need for new therapeutic approaches for problems with poor outcome , especially female loss of sexual interest The effects of three group treatment formats on 20 men with secondary erectile dysfunction and their partners were contrasted . After a comprehensive medical and psychological screening , each couple was assigned to one of three treatment groups ( Communication Technique Training , Sexual Technique Training , Combination Treatment ) or to one of two control groups ( Attention-Placebo , No-Treatment ) . Couples in the three treatment groups and the attention-placebo group participated in their respective formats in twice-weekly sessions for a total of 20 hours . The no-treatment control group received sex education and treatment after a 5-week waiting list period . All three treatment groups fostered substantial gains so that between-format differences were not statistically significant . Subject variables which predicted success/experience ratio gains included age of the male partner , perceived level of relationship adjustment , and the male partner 's success/experience ratio prior to treatment . Eighty-one percent of the treated men reached the criterion of 80 % or greater success/experience ratio ( successful penetration and subsequent ejaculation ) at the 6-month follow-up . Good nocturnal tumescence prior to treatment was correlated with a better treatment outcome than poor tumescence We admistered the International Index of Erectile Function ( IIEF ; Rosen et al. , 1997 ) question naire to 30 patients with psychogenic erectile dysfunction ( ED ) at baseline , immediately after treatment , and 3 months after treatment . We r and omized patients into three groups : group I , who had weekly sessions of time-limited theme-based group psychotherapy for 6 months and 50 mg sildenafil citrate orally on dem and ; group II , who had an intake of 50 mg sildenafl citrate orally on dem and for 6 months only ; and group III , who had weekly sessions of time-limited theme-based group psychotherapy for 6 months . We analyzed data ( 15-item IIEF ) for each group at three times during the study and compared by the data using analysis of variance ( ANOVA ) , followed by the Bonferroni multiple comparison test . We used Cochran 's Q-test for analysis between baseline and posttreatment stages of patients with remission of symptoms ( EF equal to or higher than 26 points ) . Group III had a mean score higher than group II , with the difference being statistically significant ( immediately after treatment , p = 0.033 ; at 3 months after treatment , p = 0.049 ; p < 0.05 ) . All three therapeutic alternatives result ed in an improvement of erectile function domain score . However , significant differences from baseline were observed in groups I ( p = 0.0009 ) and III ( p = 0.0002 ) but not in group II ( p = 0.135 ) . The psychotherapy groups , I and III , had significantly higher scores compared with group II , in which patients were exclusively treated with sildenafil citrate . These findings suggest that time-limited theme-based group psychotherapy is an effective treatment for psychogenic ED This study utilized a control group design to evaluate the effectiveness of group treatment of erectile dysfunction in men without partners . Twentyone men with secondary erectile dysfunction were r and omly assigned to one of two men 's groups with different cotherapy teams or to a waiting-list control condition . Results indicated that while the two men 's groups did not differ on any clinical - outcome measures , each men 's group improved significantly more than the waiting-list clients on a variety of measures concerning sexual attitudes and behaviors related to erectile dysfunction . Furthermore , most of the treatment gains for men 's group participants were maintained at six-week and six-month follow-up evaluations . However , the men 's group and waiting-list participants did not differ significantly in the reported frequency of erection difficulties following treatment . In comparing the present findings with those of previous studies of men 's group treatment , it is hypothesized that the absence of significant change in the frequency of erection difficulties in the present study may have been attributable to the older age of our clients or to the relative lack of emphasis on dating-skills training in this treatment format . This study illustrates the importance of including some form of no-treatment control condition in the evaluation of new treatments for sexual dysfunction A cohort of 45 patients diagnosed with predominant psychogenic erectile disorder ( ED ) chose couples psychotherapy . We r and omized 25 couples to also receive a vacuum constriction device ( VCD ) , also known as a vacuum erectile device , at the second session ( group 1 ) , whereas 20 couples had psychotherapy without a VCD . Twentyone couples ( 84 % ) in group 1 reported some improvement after the initial psychotherapy and VCD sessions compared with 12 of the 20 couples ( 60 % ) who reported some improvement after couples psychotherapy in group 2 . We subsequently found that 3 of the 4 couples in group 1 reporting no improvement had not used the pump provided . Early combination treatment of couples psychotherapy and a physical treatment such as a VCD may lead to a greater beneficial response in men with ED than therapy alone . The delay of demonstrating the capacity and potential benefit from a physical intervention may have a marked effect on the initial and ongoing response to sex therapy Abstract Two studies on the treatment of male sexual dysfunction are reported . In Study I , 24 couples were placed on a 6-week waiting list and subsequently treated with systematic desensitization ( SD ) or an adaptation of the Masters and Johnson method ( sex therapy , ST ) . Sexual function , satisfaction with the relationship , self-esteem and social anxiety were evaluated at the start of the waiting period , before and after treatment and in a follow-up . Both SD and ST led to improvement of sexual functioning , but a significant difference between treatments could not be demonstrated . Neither SD nor ST improved satisfaction with the relationship . In Study II , 32 couples were assigned to ST or rational emotive therapy ( RET ) . Sixteen couples dropped out of treatment . As compared with males who completed treatment , males who dropped out functioned relatively well sexually . Other differences between drop-outs and treatment-completers could not be demonstrated . In couples completing therapy , both ST and RET led to improvement of sexual functioning . Satisfaction with the relationship improved only in couples treated with RET . Significant differences between ST and RET could not be demonstrated in a valid way This study examined the effects of a sex and aging workshop highlighting permission and limited information on the sexual knowledge , attitudes , behaviors , and satisfaction of a group of older heterosexual couples experiencing erectile dysfunction . The workshop focused on disseminating information about the physiological and psychological changes that occur in the sexual response during the aging process . Twenty couples participated in this study : 10 attended a workshop and 10 served as controls . The study utilized a r and omized control group pretest/posttest design . Workshop participants completed an evaluation form and were interviewed at the time of follow-up . Data analysis revealed that the workshop participants reported significant increases in knowledge levels and in sexual satisfaction . The workshop evaluations and follow-up interviews reinforced these quantitative results . This study lends support to educational intervention as an adjunct to treatment of erectile dysfunction in the elderly population Objective To compare the acceptance of and satisfaction with intracavernosal injection ( ICI ) therapy with and without sexological counselling in men with erectile dysfunction ( ED ) This study was a controlled evaluation of men 's group treatment of erectile dysfunction that emphasized communication and dating skills training for men without partners . Following a 6-week pretreatment waiting period , 11 men were seen for 10 sessions in two men 's groups led by different cotherapy teams . Several female guest therapists attended three sessions to help the men role-play a sequence of difficult social interactions . A series of communication/dating homework assignments was added to the weekly sensual/sexual assignments . The results indicated no improvement during the waiting control period , but significant improvement on measures of sexual attitudes and behaviors following treatment . There was a significant reduction in the frequency of erection difficulties before intercourse and a trend toward reduction of erection difficulties during intercourse . These improvements were maintained over a 6-month follow-up Sixteen males with erectile failure , married or living with their partners , were assigned to either 12 bi-weekly sessions ( 6 weeks ) of Rational Emotive Therapy ( RET ) or a 6-week waiting-list control group . Active treatment administered by a graduate student in psychology with special training in RET result ed in patients making significantly more sexual intercourse attempts , reporting significantly reduced sexual anxiety , and having a significantly higher number of successful intercourse attempts than the waiting-list control group . While 6 - 9 month follow-up revealed that most treated patients had fallen back toward the pretest baseline ( lower rates of successful intercourse ) , group means as a whole were still significantly higher than pretreatment intercourse success rates . The significance of these findings are discussed |
463 | 30,079,619 | Low strength evidence suggests that mould AIT is efficacious for the treatment of respiratory allergies . | BACKGROUND Allergen immunotherapy ( AIT ) with mould extracts has been performed for many years but the final demonstration of its clinical efficacy is still missing , due to the small number of studies and their inconsistent results .
OBJECTIVE To systematic ally review efficacy and safety of AIT for the treatment of respiratory allergies to moulds . | BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents . OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a st and ardized allergen extract in a r and omized , double-blind , placebo-controlled , 3-year prospect i ve study of patients who were allergic to only Alternaria alternata . METHODS Fifty children and adolescents ( 25 girls ; 5 - 18 years of age ) with A alternata-induced seasonal allergic rhinoconjunctivitis and /or bronchial asthma were r and omly assigned to groups given treatment ( Novo-Helisen Depot , A alternata 100 % ) or placebo . The primary end point was the combined symptom medication score . Secondary end points included safety , quality of life , and sensitivity to allergen-specific nasal challenge . RESULTS Forty-five children completed the 3-year study . Although there was no significant change in year 1 , the combined symptom medication score decreased in years 2 and 3 of the study ( by 38.7 % and 63.5 % , respectively ; P < .001 for each ) . The reduction in symptoms was associated with a significant improvement in quality of life ( P < .05 ) and decrease in sensitivity after allergen-specific nasal challenge . Side effects were observed in 7 patients ; the most common ( edema at the site of injection ) occurred after 11 injections . CONCLUSIONS Allergen-specific immunotherapy with st and ardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects In this prospect i ve controlled study , 39 children with Alternaria-induced asthma and /or rhinitis were followed-up over a 3-year period . Skin tests and RAST were positive to Alternaria tenuis only . All children were treated with specific Alternaria immunotherapy . The long-term results have shown that immunotherapy was successful in 80 % of the children given more than 80.000 PNU . By contrast , the outcome of 40 selected controls also followed during the same period who did not receive immunotherapy was almost exactly the opposite . In addition to demonstrating the clinical effectivity of specific Alternaria immunotherapy , the authors stress the relationship between successful results , highest tolerated doses , and larger cumulative dosage , which is irrespective of the duration of the therapy Little knowledge is available on molds either from the environmental or clinical points of view . The latter is mainly due to the lack , until recent times , of purified and st and ardized extracts . Injective immunotherapy , largely used for patients allergic to mites and pollens , is regarded with some concern for molds . On the other h and , mold-related allergic symptoms ( i.e.,from Alternaria tenuis ) have in Italy an incidence of about 5 percent , mainly in young patients . We have therefore run a pilot study comparing the efficacy and safety of injective ( SIT ) and sublingual ( SLIT ) immunotherapy by administering the same purified and st and ardized extract of Alternaria tenuis to a total of 23 patients for two years , according to an open experimental plan . Excellent tolerance was shown to SLIT while four ( two medium- grade ) side effects appeared with SIT . Clinical improvement , subjectively stated comparing symptoms ( mainly rhinitis ) and drug consumption before and after the therapy , confirmed by an increase in the Specific Nasal Provocation threshold , was obtained with both therapies , but with a statistically significant difference in favour of SLIT . Skin reactivity and blood Alternaria tenuis specific IgE , total IgG and IgG changed in the SIT-treated group , while no statistically significant change was shown in the SLIT-treated group . These results are in good agreement with previous reports on SIT and SLIT with other inhalant allergens ( mites , grasses ) , and suggest the potential use of SLIT for Alternaria allergy , mainly in young patients , when there are concerns about the safety of and compliance with the traditional injective therapy A placebo‐controlled , double‐blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics . The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season . An aqueous preparation of a potent , biologically st and ardized and purified extract was used in a clustered dose‐increase regimen . The clinical efficacy was evaluated by a combination of symptoms ( asthma score + peak flow ) and consumption of antiasthmatic medication . The mean changes in symptoms and medication consumption over a 10–week registration period ( peak Cladosporium season ) in 1982 after 5–7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10‐week period A significant ( P= 0.03 ) difference in terms of “ improved ” , “ unchanged ” and “ deteriorated ” patients in favour of Cladosporium treatment was found . Approximately 80 % in the Cladosporium group showed improved/unchanged symptoms contrary to 30 % of the placebo treated . Side effects were observed frequently but only in the Cladosporium‐treated . About 70 % experienced a large local reaction and 100 % had episodes of asthma during dose‐increase phase . Only a few severe systemic reactions occurred . Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics A double‐blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and st and ardized Cladosporium herbarum allergen preparation . Thirty children with a clinical history suggesting mould‐induced asthma and /or rhinoconjuctivitis were included . The diagnosis was confirmed by positive skin prick test and Phadebas RAST ® as well as positive bronchial and /or conjunctival provocation test to Cladosporium herbarum . Immunotherapy was given for 10 months in a double‐blind manner to r and omized groups with either Pharmalgen ® /Cladosporium herbarum preparation or histamine placebo . Allergic side effects to injections were common , especially during the peak of the mould season ( July‐September in Sc and inavia ) . In the active group , 13/16 patients experienced general reactions during the first 10 months of treatment . After 6 months of treatment , eye , nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups , maybe because most of the children were also sensitive to many other allergens , including Alternaria alternala . However , medication scores were significantly lower in the treated group ( P < 0.01 ) . Bronchial ( P < 0.01 ) and conjunctival sensitivity ( P= 0.01 ) were significantly reduced in the Cladosporium‐treated group but not in the placebo group after 10 mouths of treatment . This is the first double‐blind clinical trial showing the clinical efficacy of immunotherapy in children with mould‐induced asthma Studies of immunotherapy with oral Alternaria extracts are scarce . We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy , aged between 7 and 17 years , who are also sensitized extract was used . Allergic activity was determined through RAST inhibition and skin prick test . Quantification of the principal allerten ( Alt a 1 ) was performed through the 2-site binding assay , with a mean content of 34.2 ng Alt a 1/micro g protein . The parameters analyzed were the symptom-medication score , skin prick using the end-point technique , specific bronchial challenge test , peak flow , total and specific IgE and IgG4 . Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment . The initial phase of immunotherapy lasted 3 months until the maximum dose was reached . This was maintained for 12 months ; the mean accumulated dos was 280,000 PNU . Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy . No differences were found in the control group . Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered . All adverse reactions were mild-to-moderate . In the treated group , papule size was significantly reduced . Values for the specific bronchial challenge test , expressed through PD20 , were significantly higher in the immunotherapy group . Peak flow showed no changes in either group . Values of IgG4 were significantly higher in the immunotherapy group . Total and specific IgE levels showed no significant changes in either group . In conclusion , oral immunotherapy with Alternaria extract is clinical ly effective in pediatric patients . In general , the therapy was well tolerated . It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4 , wich are implicated in humoral response INTRODUCTION Sensitisation to Alternaria is a cause of respiratory disease in Spain , particularly in childhood , but it is also a significant marker of the severity of this disease . Therefore , the use of an aetiological treatment ( allergen specific immunotherapy ) is essential , and both subjective and objective clinical parameters should be used to follow up this treatment . OBJECTIVE This open-label , uncontrolled , observational , prospect i ve study was design ed in order to study the evolution of these patients on allergen specific immunotherapy therapy in daily clinical practice and to assess the use of different monitoring tools . MATERIAL AND METHODS A total of 99 patients were included . They were monosensitised to this perennial allergen and treated with subcutaneous allergen specific immunotherapy . After one year of follow-up , these patients were assessed for the presence of symptoms , use of medication , clinical incidents , quality of life and asthma control . RESULTS After one year of treatment a significant fall was observed in the use of concomitant medication ( β2-agonists : p=0.0278 , inhaled corticosteroids : p=0.0007 , anti-leukotrienes : p=0.0495 ) , nasal symptoms ( p=0.0081 ) , quality of life ( PAQLQ , p<0.0001 ) and asthma control ( ACQ , p<0.0001 ) . Twenty-one patients had to attend emergency department due to exacerbation of their allergic disease , and only one of them had to be admitted to hospital . CONCLUSION respiratory allergic disease due to Alternaria alternata is a disease which is hard to control , and in our daily practice , the use of specific subcutaneous immunotherapy can be of significant benefit in our paediatric patients Allergen-specific immunotherapy ( ASIT ) with fungal extracts has been beset by safety and efficacy problems , which result mainly from qualitative and quantitative variations . Little has been published on the safety and efficacy of these extracts . The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract . A total of 28 patients were selected with rhinitis and /or bronchial asthma because of Alternaria allergy and monosensitization to molds . The patients were r and omized to an active ASIT or placebo group , both groups on a conventional immunotherapy schedule ( increasing weekly doses until maintenance dose and then monthly doses ) . Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system . Clinical efficacy was analyzed for a year with symptom/medication diary cards , peak expiratory flow ( PEF ) measures , clinical severity score , severity of symptoms ( visual analog scale ) , subjective evaluation of treatment by the patient and the physician , and a quality of life question naire . Twenty-three patients completed the study ; all reached the established maintenance dose with only two mild adverse reactions in the whole sample . Significant improvements were found after 6 months in respiratory symptoms in the active treatment group , and in all symptoms in both groups . PEF increased significantly in the active treatment group but not in the placebo group . The severity of asthma decreased in the active treatment group , and the severity of rhinitis decreased in both groups . Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group , but only after 12 months in the placebo group . Physicians judged the disease course as significantly better in the active treatment group . ASIT with the A. alternata extract was safe , with clinical improvements after one year of treatment BACKGROUND Respiratory allergy due to Alternaria is a relevant clinical problem , and specific immunotherapy may represent a viable treatment option . Sublingual immunotherapy ( SLIT ) is safe and effective , but data for Alternaria are lacking . OBJECTIVE To assess the efficacy of st and ardized SLIT in patients sensitized to Alternaria in a r and omized , prospect i ve , double-blind , placebo-controlled trial . METHODS Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled . After a baseline season , SLIT or matched placebo was given for 10 months . Symptoms and rescue medication intake were recorded on diary cards between June and October . Skin prick testing was performed and specific IgE , IgG4 , and precipitin levels were measured at baseline and at the end of the study . RESULTS Twenty-seven patients ( age range , 14 - 42 years ) were r and omized , and 26 completed the study . The baseline characteristics were homogeneous in the 2 groups . After treatment , patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season , whereas no change was seen in the placebo group . Skin prick test reactivity significantly decreased only in the SLIT group . No change was seen in specific IgG4 levels in the 2 groups , whereas Alt a 1 specific IgE levels significantly increased in the active group . One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment . CONCLUSION SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria The efficacy and safety of terfenadine in the management of hay fever were compared with those of cetirizine in a multicenter , double-blind , parallel-group study , carried out during the 1990 spring pollen season . The patients were r and omly assigned to one of two groups of treatment , 70 patients being given terfenadine 120 mg , and 72 patients cetirizine 10 mg , once daily for 7 days . The severity of the main symptoms was evaluated at baseline and after treatment by a 4-point rating scale . In addition , the overall symptom severity was recorded daily by the patient on a diary card . Both terfenadine and cetirizine produced significant relief of symptoms by the end of treatment , with a decrease in symptom severity ranging from 46 to 69 % for terfenadine and from 40 to 55 % for cetirizine . Adverse effects experienced by terfenadine- and cetirizine-treated patients were mainly drowsiness , with minor differences between the two groups . The results of this study confirmed previous experiences , showing that both terfenadine and cetirizine once daily should be regarded as effective drugs for the management of hay fever Abstract Background : Alternaria alternata ( AA ) sensitisation is a common cause of respiratory allergies such as rhinitis and asthma . So far there are no controlled double-blind trials evaluating the efficacy and safety of specific sublingual immunotherapy ( SLIT ) in AA allergies . Objective : To evaluate the efficacy of SLIT treatment in terms of clinical improvement and rescue medication usage in patients with confirmed AA respiratory allergy . Subjects and methods : A r and omised , parallel group study in 52 subjects was conducted ( 32 men , mean age 20 ± 9 years ) with clinical ly- and laboratory-confirmed AA respiratory allergies ( allergic rhinitis with or without mild-to-moderate asthma ) . Patients were r and omly assigned to SLIT treatment ( SLITone Alternaria , ALK-Abellò , Denmark ) one vial per day without up-dosing for 3 consecutive years ( n = 34 ) or to a control group ( n = 18 ) with a r and om allocation ratio of 2:1 . Clinical improvement was assessed by evaluating patient-reported outcome ( PRO ) using a 6 cm visual analogue scale ( 0 : extreme worsening ; 3 : no change ; 6 : extreme improvement ) . The VAS score was evaluated every year with an intra- and inter-group comparison . Rescue medication score ( MS ) was assessed by evaluating symptomatic drug consumption . Results : After 3 years the VAS score was 4.7 ± 0.8 in the SLIT group and 2 ± 1.6 in the control group ( p = 0.0002 ) . Clinical improvement was observed in 33 out of 34 subjects in the SLIT group ( 97 % ) and in 5 out of 18 in the control group ( 27 % ) ( p = 0.0001 ; Fisher 's exact test ) . The MS significantly ( p = 0.0001 ) decreased in the SLIT group from 4.3 to 1.7 at the end of 3 years ’ treatment . In the control group MS increased from 3.4 to 4.0 by the end of the trial . No serious adverse events were observed in the either group . Six patients in the SLIT group ( 17 % ) reported side-effects , in general mild and transient . One patient prematurely discontinued the treatment due to gastrointestinal discomfort . Conclusion : The current study has shown that a 3-year course of SLIT is efficacious and well-tolerated in subjects with AA respiratory allergies |
464 | 30,202,382 | These findings indicate that interventions in active travel and classrooms setting s positively influence youth PA . | null | null |
465 | 30,536,919 | Trials show that the immediate technical success rate of restoring luminal patency is higher in the stent group but reveal no clear differences in short-term patency at six months between infrapopliteal arterial lesions treated with PTA with stenting versus those treated with PTA without stenting .
We ascertained no clear differences between groups in periprocedural complications , major amputation , and mortality .
However , use of different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication and the duration of its use within and between trials may have influenced the outcomes . | BACKGROUND Chronic limb-threatening ischaemia ( CLTI ) is a manifestation of peripheral arterial disease ( PAD ) that includes chronic ischaemic rest pain or ischaemic skin lesions , ulcers , or gangrene for longer than two weeks .
The severity of the disease depends on the extent of arterial stenosis and the availability of collateral circulation .
Treatment for CLTI aims to relieve ischaemic pain , heal ischaemic ulcers , prevent limb loss , improve quality of life , and prolong survival .
CLTI due to occlusive disease in the infrapopliteal arterial circulation ( below-knee circulation ) can be treated via an endovascular technique by a balloon opening the narrowed vessel , so called angioplasty , with or without the additional deployment of a scaffold made of metal alloy or other material , so called stenting .
Endovascular interventions in the infrapopliteal vasculature may improve symptoms in patients with CLTI by re-establishing in-line blood flow to the foot .
Controversy remains as to whether a balloon should be used alone to open the vessel , or whether a stent should also be deployed .
OBJECTIVES To determine the efficacy and safety of percutaneous transluminal angioplasty ( PTA ) alone versus PTA with stenting of infrapopliteal arterial lesions ( anterior tibial artery , posterior tibial artery , fibular artery ( formerly known as peroneal artery ) , and common tibioperoneal trunk ) for patients with chronic limb-threatening ischaemia ( CLTI ) . | Purpose : To determine the primary success and short-term patency of stent application as a primary treatment modality for high- grade lesions of the infrapopliteal arteries compared with treatment with percutaneous transluminal angioplasty ( PTA ) in critical limb ischemia in a r and omized prospect i ve study . Methods : Endovascular therapy was performed on 95 lesions in 51 patients ( mean age 72.0 years , range 47–80 years ) who presented clinical ly with Fontaine stages III and IV . One patient underwent treatment in both limbs . After angiographic lesion identification , patients were r and omized for treatment by PTA ( 53 lesions in 27 patients ) or stent application ( 42 lesions in 24 patients ) . Follow-up by clinical investigation and conventional angiography or spiral CT angiography was performed in 37 patients ( 57 lesions ) 6 to 12 months after the procedure , or when clinical ly indicated . Evaluation was performed by two observers , double-blinded , with thresholds for lesion restenosis of 50 % and 70 % . Statistical evaluation was performed on a lesion basis by Kaplan – Meier estimated probability rates , and log-rank and Wilcoxon tests . The primary endpoint was the angiographic patency rate of treated lesions . Results : The inter-reader agreement was high ( κ = 0.82 ) . For the stent group the cumulative primary patency at 6 months was 83.7 % at the 70 % restenosis threshold , and 79.7 % at the 50 % restenosis threshold . For PTA , the primary patency at 6 months was 61.1 % at the 70 % restenosis threshold and 45.6 % at the 50 % restenosis threshold . Both results were statistically significant ( p < 0.05 ) . Conclusion : Infrapopliteal stent application is an effective treatment modality for high- grade lesions in chronic critical limb ischemia . Compared with PTA , higher patency rates can be expected after 6 months Background —Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty ( PTA ) and bail-out bare metal stenting ( BMS ) is hampered by restenosis . In interventional cardiology , drug-eluting stents ( DES ) have shown better patency rates and are st and ard practice nowadays . An investigator-initiated , multicenter , r and omized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions . Methods and Results —Adults with critical limb ischemia ( Rutherford category ≥4 ) and infrapopliteal lesions were r and omized to receive PTA±BMS or DES with paclitaxel . Primary end point was 6-month primary binary patency of treated lesions , defined as ⩽50 % stenosis on computed tomographic angiography . Stenosis > 50 % , retreatment , major amputation , and critical limb ischemia – related death were regarded as treatment failure . Severity of failure was assessed with an ordinal score , ranging from vessel stenosis through occlusion to the clinical failures . Seventy-four limbs ( 73 patients ) were treated with DES and 66 limbs ( 64 patients ) received PTA±BMS . Six-month patency rates were 48.0 % for DES and 35.1 % for PTA±BMS ( P=0.096 ) in the modified-intention-to-treat and 51.9 % and 35.1 % ( P=0.037 ) in the per- protocol analysis . The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES ( P=0.041 ) . The observed major amputation rate remained lower in the DES group until 2 years post-treatment , with a trend toward significance ( P=0.066 ) . Less minor amputations occurred after DES until 6 months post-treatment ( P=0.03 ) . Conclusions —In patients with critical limb ischemia caused by infrapopliteal lesions , DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00471289 The study was design ed as a feasibility trial to evaluate the use of GP IIb/IIIa blockade in connection with drug eluting stents , bare stents and PTA only . Sixty patients with current ulcers were r and omly assigned to receive abciximab plus a sirolimus coated stent ( N.=14 ) , abciximab plus a bare stent ( N.=16 ) , abciximab plus PTA ( N.=14 ) and PTA alone ( N.=19 ) . Angiographic control was performed at two and six months . Recanalization was successful in all cases . Two month restenosis rate was 9 % , 45.5 % , 67 % and 46 % . At six month follow-up restenosis rate was 9 % , 67 % , 75 % and 58 % , respectively ; 14 % of all patients had major amputations within six months . Adjunctive administration of abciximab during peripheral arterial intervention below the knee was found to be safe . Sirolimus coated stent administration was followed by a higher patency rate BACKGROUND The Bypass versus Angioplasty in Severe Ischaemia of the Leg ( BASIL ) trial showed in patients with severe lower limb ischemia ( rest pain , tissue loss ) who survive for 2 years after intervention that initial r and omization to bypass surgery , compared with balloon angioplasty , was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months , respectively . The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic ( angiographic ) patterns of disease . METHODS Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus ( TASC ) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes . RESULTS As was to be expected from the r and omization process , patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II . In patients with the least overall disease , it tended to be concentrated in the superficial femoral and popliteal arteries , which were the commonest sites of disease overall . The below knee arteries became increasingly involved as the overall severity of disease increased , but the disease in the above knee arteries did not tend to worsen . The posterior tibial artery was the most diseased crural artery , whereas the peroneal appeared relatively spared . There was less interobserver disagreement with the Bollinger method than with the TASC II classification system , which also appears inherently less sensitive to clinical ly important differences in infrapopliteal disease among patients with severe leg ischemia . CONCLUSIONS Anatomic ( angiographic ) disease description in patients with severe leg ischemia requires a reproducible scoring system that is sensitive to differences in crural artery disease . The Bollinger system appears well suited for this purpose , but the TASC II classification system less so . We hope this detailed analysis will facilitate appropriate generalization of the BASIL trial data to other groups of patients affected by similar anatomic ( angiographic ) patterns of disease OBJECTIVES The study investigated the efficacy and safety of a balloon exp and able , sirolimus-eluting stent ( SES ) in patients with symptomatic infrapopliteal arterial disease . BACKGROUND Results of infrapopliteal interventions using balloon angioplasty and /or bare stents are limited by a relatively high restenosis rate , which could be potentially improved by stabilizing the lesion with a SES . METHODS Two hundred patients ( total lesion length 27 ± 21 mm ) were r and omized to infrapopliteal SES stenting or percutaneous transluminal balloon angioplasty ( PTA ) . The primary endpoint was 1-year in-segment binary restenosis by quantitative angiography . RESULTS Ninety-nine and 101 patients ( mean age 73.4 years ; 64 % diabetics ) were r and omized to SES and PTA , respectively ( 8 crossover bailout cases to SES ) . At 1 year , there were lower angiographic restenosis rates ( 22.4 % vs. 41.9 % , p = 0.019 ) , greater vessel patency ( 75.0 % vs. 57.1 % , p = 0.025 ) , and similar death , repeat revascularization , index-limb amputation rates , and proportions of patients with improved Rutherford class for SES versus PTA . CONCLUSIONS SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease Purpose : To report the 1-year angiographic and clinical outcome from a prospect i ve single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia ( CLI ) who underwent below-the-knee endovascular revascularization . Methods : Stenting was performed as a bailout procedure for suboptimal angioplasty results ( flow-limiting dissection , elastic recoil , or postangioplasty residual stenosis > 30 % ) . In the first 29 patients , infrapopliteal stenting was performed with bare metal stents ( group B ) and with sirolimus-eluting stents in the other 29 patients ( group S ) . Results : Below-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities ( hyperlipidemia and symptomatic cardiac and carotid disease ) were more pronounced in group S ( p<0.05 ) . At 6 months , sirolimus-eluting stents demonstrated significantly higher primary patency ( OR 5.625 , 95 % CI 1.711 to 18.493 , p=0.004 ) and decreased in-stent binary restenosis ( OR 0.067 , 95 % CI 0.021 to 0.017 , p<0.001 ) and in-segment binary restenosis ( OR 0.229 , 95 % CI 0.099 to 0.533 , p=0.001 ) . After 1 year , sirolimus-eluting stents were steadily associated with increased primary patency ( OR 10.401 , 95 % CI 3.425 to 31.589 , p<0.001 ) and significantly less in-stent ( OR 0.156 , 95 % CI 0.060 to 0.407 , p<0.001 ) and in-segment ( OR 0.089 , 95 % CI 0.023 to 0.349 , p=0.001 ) binary restenosis . In addition , sirolimus-eluting stents were associated with significantly fewer cumulative target lesion re interventions at 6 months ( OR 0.057 , 95 % CI 0.008 to 0.426 , p=0.005 ) and 1 year ( OR 0.238 , 95 % CI 0.067 to 0.841 , p=0.026 ) . No significant differences between groups B and S were noted at 1 year with respect to mortality ( 10.3 % versus 13.8 % , respectively ) , minor amputation ( 17.2 % versus 10.3 % ) , or limb salvage ( 100 % versus 96 % ) . Conclusion : The application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment Excellent results with small stents in coronary arteries have led endovascular therapists to their use in infrapopliteal vessels . However , to date no level I evidence exists to recommend primary stenting over infrapopliteal angioplasty alone . The aim of this r and omized single-center trial was to compare their 1-year outcome . A total of 38 limbs in 35 patients with critical limb ischemia were r and omized to angioplasty ( 22 pts ) or primary stenting ( 16 pts ) . Target lesions were infrapopliteal occluded ( 36 ) or stenotic ( 20 ) lesions ranging from < 2 to > 15 cm in length . The mean age was 72 years . At 12 months , there was no statistical difference in survival ( angioplasty , 69.3 % ; primary stenting , 74.7 % ) , in limb salvage ( angioplasty , 90 % ; primary stenting , 91.7 % ) , or in primary and secondary patency ( angioplasty , 66 and 79.5 % ; primary stenting , 56 and 64 % ) between the groups Renal insufficiency was the only significant negative predicting factor for limb salvage in both groups . In conclusion , the 1-year results for both groups were broadly similar . Stenting has its place in infrapopliteal angioplasty if the procedure is jeopardized by a dissection or recoil , but our results do not support primary stenting in all cases Background Clinical outcomes reported after treatment of infrapopliteal lesions with drug‐eluting stents ( DESs ) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent ( PTA‐BMS ) through midterm follow‐up in patients with critical limb ischemia . In the present study , long‐term results of treatment of infrapopliteal lesions with DESs are presented . Methods and Results Adults with critical limb ischemia ( Rutherford category ≥4 ) and infrapopliteal lesions were r and omized to receive PTA‐BMS or DESs with paclitaxel . Long‐term follow‐up consisted of annual assessment s up to 5 years after treatment or until a clinical end point was reached . Clinical end points were major amputation ( above ankle level ) , infrapopliteal surgical or endovascular reintervention , and death . Preserved primary patency ( ≤50 % restenosis ) of treated lesions was an additional morphological end point , assessed by duplex sonography . In total , 74 limbs ( 73 patients ) were treated with DESs and 66 limbs ( 64 patients ) were treated with PTA‐BMS . The estimated 5‐year major amputation rate was lower in the DES arm ( 19.3 % versus 34.0 % for PTA‐BMS ; P=0.091 ) . The 5‐year rates of amputation‐ and event‐free survival ( survival free from major amputation or reintervention ) were significantly higher in the DES arm compared with PTA‐BMS ( 31.8 % versus 20.4 % , P=0.043 ; and 26.2 % versus 15.3 % , P=0.041 , respectively ) . Survival rates were comparable . The limited available morphological results showed higher preserved patency rates after DESs than after PTA‐BMS at 1 , 3 , and 4 years of follow‐up . Conclusions Both clinical and morphological long‐term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA‐BMS . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT00471289 OBJECTIVES This study sought to report the results of a prospect i ve r and omized controlled trial comparing paclitaxel-coated balloons ( PCB ) versus drug-eluting stents ( DES ) in long infrapopliteal lesions . BACKGROUND DES have an established role in the treatment of short infrapopliteal lesions , whereas there is increasing evidence for the use of PCB in longer below-the-knee lesions . METHODS Inclusion criteria were patients with Rutherford classes 3 to 6 and angiographically documented infrapopliteal disease with a minimum lesion length of 70 mm . The primary endpoint was target lesion restenosis > 50 % assessed by digital angiography at 6 months . Secondary endpoints included immediate post-procedure stenosis and target lesion revascularization . RESULTS Fifty patients were r and omized to undergo infrapopliteal PCB angioplasty ( 25 arteries in 25 limbs ; PCB group ) or primary DES placement ( 30 arteries in 27 limbs ; DES group ) . Immediate residual post-procedure stenosis was significantly lower in DES ( 9.6 ± 2.2 % vs. 24.8 ± 3.5 % in PCB ; p < 0.0001 ) . At 6 months , 5 patients died ( 2 in PCB vs. 3 in DES ; p = 1.00 ) and 3 suffered a major amputation ( 1 in PCB vs. 2 in DES ; p = 1.00 ) . In total , 44 angiograms were evaluable with quantitative vessel analysis . Binary ( > 50 % ) angiographic restenosis rate was significantly lower in DES ( 7 of 25 [ 28 % ] vs. 11 of 19 [ 57.9 % ] in PCB ; p = 0.0457 ) . There were no significant differences with regard to target lesion revascularization ( 2 of 26 [ 7.7 % ] in DES vs. 3 of 22 [ 13.6 % ] in PCB ; p = 0.65 ) . Positive vessel wall remodeling was observed in 3 cases in the PCB arm ( 3 of 19 [ ( 15.8 % ) ] vs. 0 of 19 [ 0 % ] in DES ; p = 0.07 ) . CONCLUSIONS Compared with PCB in long infrapopliteal lesions , DES are related with significantly lower residual immediate post-procedure stenosis and have shown significantly reduced vessel restenosis at 6 months . PCB may produce positive vessel remodeling . ( Infrapopliteal Drug-Eluting Angioplasty Versus Stenting [ IDEAS-I ] ; NCT01517997 ) BACKGROUND Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease . We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences . METHODS We enrolled 352 patients in whom one coronary artery required treatment , with diameter 2.5 - 3.0 mm and lesion length 15 - 32 mm . We r and omly assigned patients sirolimus-eluting stents ( n=175 ) or bare-metal stents ( control , n=177 ) . At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion ( restenosis of > or = 50 % diameter , including 5 mm vessel segments proximal and distal to stented segment ) . Patients were also followed up for 9 months for major adverse cardiac events . Analysis was by intention to treat . FINDINGS Stent implantation was successful in 100 % of sirolimus-stent patients and 99.4 % of controls . The mean diameter of treated coronary arteries was 2.55 mm ( SD 0.37 ) and mean lesion length was 15.0 mm ( 6.0 ) . Multiple stents were implanted in 170 ( 48 % ) patients . At 8 months , minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents ( 2.22 vs 1.33 mm , p<0.0001 ) . The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents ( 5.9 vs 42.3 % , p=0.0001 ) . Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls ( 8.0 vs 22.6 % , p=0.0002 ) , due mainly to a lower need for target-lesion revascularisations ( 4.0 vs 20.9 % , p<0.0001 ) . INTERPRETATION Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter BACKGROUND In endovascular recanalisation of infrapopliteal arteries , studies have already pointed out the value of balloon angioplasty , but for stent implantation very few r and omized controlled data exist so far . PATIENTS AND METHODS We conducted a r and omized controlled prospect i ve trial in patients with critical limb ischemia ( CLI ) comparing the effect of percutaneous transluminal balloon angioplasty ( PTA ) versus primary stenting in infrapopliteal arteries , concerning 1-year clinical benefit and reobstruction rate . RESULTS 54 patients were either r and omized for primary stenting ( balloon exp and able stent ) or PTA alone , 33 patients were assigned to the PTA group , 21 patients to the stent group . The whole follow up period of 12 months was completed by 46 patients . Improvement by at least one Rutherford classification was reached by a total of 33 ( 75.0 % ) of patients at month 12 , 22 ( 81.5 % ) in the PTA group and 11 ( 64.7 % ) in the stent group . A complete ulcer healing at month 12 showed 21 ( 63.6 % ) of all patients , with a higher percentage in patients treated with PTA alone 16 ( 80.0 % ) vs 5 ( 38.5 % ) . 50.0 % of all patients showed re-obstruction over the follow-up period , 39.4 % of the PTA and 66.7 % of the stent group . At month 3 primary patency rate was nearly equal in both groups ( 76.7 % PTA vs 75.0 % stent ) , but drifted apart with the duration of the follow-up period , with a primary patency at month 12 in the PTA group of 48,1 % vs 35,3 % in the stent group . As for secondary patency at month 12 the PTA group showed a patency rate of 70.4 % , vs 52.9 % in the stent group . CONCLUSIONS Primary stenting with balloon exp and able stents in the infrapopliteal arteries does not outway the benefit of PTA alone with the application of modern hydrophilic balloon catheters in patients with CLI The Percutaneous transluminal Angioplasty and Drug eluting stents for Infrapopliteal lesions in critical limb ischemia ( PADI ) trial is a prospect i ve , multicenter , r and omized , controlled , double-arm study investigating the safety and efficacy of primary paclitaxel-eluting stent implantation vs primary percutaneous transluminal angioplasty ( PTA ) in infrapopliteal lesions in critical limb ischemia ( CLI ) . PTA with provisional " bailout " stent implantation is currently an accepted treatment for arterial obstructions in CLI , including those in below-the-knee arteries . A drawback compared to open bypass surgery is the relatively high restenosis rate . One proposed method to reduce restenosis is the use of drug-eluting stents ( DES ) , as these have shown good results in the coronary bed . Primary DES implantation for focal obstructions in infrapopliteal arteries in CLI potentially reduces restenosis compared to PTA alone and may subsequently prolong effect of treatment , allowing for better wound healing , and preventing recurrence of symptoms . In this article , we report on rationale , design , and progress of the PADI trial , which investigates the safety and efficacy of a paclitaxel-eluting stent system compared to PTA with provisional bare metal stent implantation Purpose : To compare primary placement of a self-exp and ing nitinol stent to percutaneous transluminal angioplasty ( PTA ) with bailout stenting in infrapopliteal arteries of patients with severe intermittent claudication or critical limb ischemia ( CLI ) . Methods : In the EXP AND trial ( Clinical Trials.gov ; identifier NCT00906022 ) , 92 patients ( mean age 72.9±9.5 years ; 62 men ) undergoing treatment for infrapopliteal stenosis in 11 European centers were r and omized 1:1 to either self-exp and ing nitinol stenting with the Astron Pulsar/Pulsar-18 nitinol stent or PTA with bailout stenting . The primary endpoint was sustainable clinical improvement after 12 months , defined as a ≥1-category increase for Rutherford category 3 patients or a ≥2-category increase for CLI patients ( Rutherford categories 4/5 ) compared with baseline . Furthermore , target lesion revascularization ( TLR ) , mortality , and amputation were assessed after 12 months . Results : Sustained clinical improvement at 1 year was observed in 74.3 % of the patients treated with primary stenting and in 68.6 % of the patients treated with PTA and bailout stenting ( p>0.05 ) . Kaplan-Meier estimates of freedom from TLR ( 76.6 % and 77.6 % ) , mortality ( 7.4 % vs 2.1 % ) , and amputation [ 8.9 % ( major 6.7 % ) vs 13.2 % ( major 8.7 % ) ] at 1 year were not significantly different . Conclusion : Primary self-exp and ing nitinol stenting did not show statistically different clinical outcomes compared to angioplasty with bailout stenting for infrapopliteal lesions BACKGROUND The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization . Because sirolimus ( rapamycin ) inhibits the proliferation of lymphocytes and smooth-muscle cells , we compared a sirolimus-eluting stent with a st and ard uncoated stent in patients with angina pectoris . METHODS We performed a r and omized , double-blind trial to compare the two types of stents for revascularization of single , primary lesions in native coronary arteries . The trial included 238 patients at 19 medical centers . The primary end point was in-stent late luminal loss ( the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months ) . Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis ( luminal narrowing of 50 percent or more ) . We also analyzed a composite clinical end point consisting of death , myocardial infa rct ion , and percutaneous or surgical revascularization at 1 , 6 , and 12 months . RESULTS At six months , the degree of neointimal proliferation , manifested as the mean ( + /-SD ) late luminal loss , was significantly lower in the sirolimus-stent group ( -0.01+/-0.33 mm ) than in the st and ard-stent group ( 0.80+/-0.53 mm , P<0.001 ) . None of the patients in the sirolimus-stent group , as compared with 26.6 percent of those in the st and ard-stent group , had restenosis of 50 percent or more of the luminal diameter ( P<0.001 ) . There were no episodes of stent thrombosis . During a follow-up period of up to one year , the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the st and ard-stent group ( P<0.001 ) . The difference was due entirely to a higher rate of revascularization of the target vessel in the st and ard-stent group . CONCLUSIONS As compared with a st and ard coronary stent , a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation , restenosis , and associated clinical events OBJECTIVES The authors sought to report the wound healing outcomes , health-related quality -of-life changes and quality -adjusted life-years ( QALYs ) gain in the 2 treatment arms of the ACHILLES ( Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease ) multicenter r and omized trial . BACKGROUND The ACHILLES r and omized trial has previously shown that sirolimus-eluting stents ( SES ) may achieve lower vessel restenosis and higher event-free survival rates compared with plain balloon angioplasty ( PTA ) for infrapopliteal lesions . METHODS A total of 200 patients were r and omly assigned between SES and PTA for the treatment of infrapopliteal arterial occlusive lesions . Progression of wound healing was serially assessed by digital photography . Health-related quality -of-life scores were assessed with the self-administered EQ-5D question naire up to 1 year from r and omization . QALYs gained were calculated with a st and ard multiplicative model using distribution-free Bayesian modeling . RESULTS In total , 109 open wounds ( n = 54 in SES ; n = 55 in PTA ) were documented at baseline . At 6 months , wound volume reduction ( % ) was significantly higher in the SES group ( 95 % healing [ 95 % confidence interval ( CI ) : 80 % to 99 % ] compared with 60 % healing [ 95 % CI : 13 % to 90 % ] in the PTA group ; p = 0.048 ) . At 1 year , rates of complete wound closure were higher in the case of SES ( 72.9 % vs. 55.6 % closed wounds in PTA ; p = 0.088 ) . The recorded weighted EQ-5D score improved significantly up to 1 year in case of SES ( p < 0.0001 ) , but not in case of PTA . There was a trend of more QALYs gained with SES compared with PTA up to 1 year after r and omization . Relative QALY gain was 0.10 ( 95 % CI : -0.01 to 0.21 ; p = 0.08 ) in the whole study and 0.17 ( 95 % CI : -0.03 to 0.35 ; p = 0.09 ) in the wound subgroups comparison . CONCLUSIONS Infrapopliteal SES accelerates wound healing and may improve quality of life compared with PTA . ( Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease [ ACHILLES ] ; NCT00640770 ) PURPOSE To determine the clinical outcome and the success of stent application for high- grade lesions of the infrapopliteal arteries compared with treatment with percutaneous transluminal angioplasty ( PTA ) in critical limb ischemia ( CLI ) . MATERIAL S AND METHODS In this ethics board-approved r and omized prospect i ve study , PTA or stent application was performed on 131 lesions in 88 patients with CLI . The primary end points were clinical improvement after endovascular treatment and limb salvage rate . Secondary end points were defined by the minimal lumen diameter ( MLD ) before and after the revascularization procedure , percentage of residual diameter stenosis ( DS ) , binary restenosis rate ( > 50 % DS and > 70 % DS ) , and incidence of target lesion revascularization at 9-month follow-up . RESULTS At 3 months , the clinical status in the PTA group was less improved than that in the stent group ( P = .008 ) . At 9 months , there had been five minor and two major amputations in the PTA group and five major and five minor amputations in the stent group . MLD was significantly larger and the percentage of DS was significantly less in the stent group at completion angiography . At 9 months , the angiographic control showed better trends for the stent group in comparison to the PTA group despite that no significant differences were detected ( MLD , 1.19 mm ± 0.92 vs 1.02 mm ± 1.02 ; DS , 38.68 % ± 25.47 vs 43.31 % ± 28.37 ) . CONCLUSION Infrapopliteal stent application is an effective treatment modality in CLI . The PTA and stent groups were essentially equal at 3 and 9 months except for the difference in clinical improvement in the stent group at 3 months BACKGROUND Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization . METHODS We conducted a r and omized , double-blind trial comparing a sirolimus-eluting stent with a st and ard stent in 1058 patients at 53 centers in the United States who had a newly diagnosed lesion in a native coronary artery . The coronary disease in these patients was complex because of the frequent presence of diabetes ( in 26 percent of patients ) , the high percentage of patients with longer lesions ( mean , 14.4 mm ) , and small vessels ( mean , 2.80 mm ) . The primary end point was failure of the target vessel ( a composite of death from cardiac causes , myocardial infa rct ion , and repeated percutaneous or surgical revascularization of the target vessel ) within 270 days . RESULTS The rate of failure of the target vessel was reduced from 21.0 percent with a st and ard stent to 8.6 percent with a sirolimus-eluting stent (P<0.001)--a reduction that was driven largely by a decrease in the frequency of the need for revascularization of the target lesion ( 16.6 percent in the st and ard-stent group vs. 4.1 percent in the sirolimus-stent group , P<0.001 ) . The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents , as assessed by both angiography and intravascular ultrasonography . Subgroup analyses revealed a reduction in the rates of angiographic restenosis and target-lesion revascularization in all subgroups examined . CONCLUSIONS In this r and omized clinical trial involving patients with complex coronary lesions , the use of a sirolimus-eluting stent had a consistent treatment effect , reducing the rates of restenosis and associated clinical events in all subgroups analyzed |
466 | 30,815,258 | Elastic resistance training is able to promote similar strength gains to conventional resistance training , in different population profiles and using diverse protocol | Given the practicality and low cost of using elastic resistance in training for different population s and its effectiveness in a range of outcomes , a comparison with conventional devices could clarify and quantify the benefits provided by both mode .
To compare the effects of resistance training with elastic devices ( tubes and Thera-B and s ) and conventional devices ( weight machines and dumbbells ) on the outcome muscular strength . | The aim of this study was to assess effects of a short-term resistance program on strength in fit young women using weight machines/free weights or elastic tubing . 42 physically fit women ( 21.79±0.7 years ) were r and omly assigned to the following groups : ( i ) the Thera-B and ( ® ) Exercise Station Group ( TBG ) ; ( ii ) the weight machines/free weights group ( MFWG ) ; or ( iii ) the control group ( CG ) . Each experimental group performed the same periodised training program that lasted for 8 weeks , with 2 - 4 sessions per week and 3 - 4 sets of 8 - 15 submaximal reps . A load cell ( Isocontrol ; ATEmicro , Madrid , Spain ) was used to test the evolution of the Maximum Isometric Voluntary Contraction ( MIVC ) in 3 different exercises : Vertical Rowing ( VR ) , Squat ( S ) and Back Extension ( BE ) . A mixed model MANOVA [ group ( CG , TBG , MFWG ) x testing time ( pre-test , post-test ) ] was applied to determine the effect of the different resistance training devices on strength . The only groups to improve their MIVC ( p<0.005 ) were TBG and MFWG , respectively : VR 19.87 % and 19.76 % ; S 14.07 and 28.88 ; BE 14.41 % and 14.00 % . These results indicate that resistance training using elastic tubing or weight machines/free weights have equivalent improvements in isometric force in short-term programs applied in fit young women Objective : To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity , muscle strength , fat-free mass , and systemic inflammation in patients with chronic obstructive pulmonary disease . Design : A prospect i ve , r and omized , eight-week clinical trial . Setting : The study was conducted in a university-based , outpatient , physical therapy clinic . Subjects : A total of 49 patients with moderate chronic obstructive pulmonary disease . Interventions : Participants were r and omly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks . Main measures : The primary outcome measure was functional exercise capacity . The secondary outcome measures were peripheral muscle strength , health-related quality of life assessed by the Chronic Respiratory Disease Question naire ( CRDQ ) , fat-free mass , and cytokine profile . Results : After eight weeks , the mean distance covered during six minutes increased by 73 meters ( ±69 ) in the elastic tubing group and by 42 meters ( ±59 ) in the conventional group ( p < 0.05 ) . The muscle strength and quality of life improved in both groups ( P < 0.05 ) , with no significant differences between the groups . There was a trend toward an improved fat-free mass in both groups ( P = 0.05 ) . After the first and last sessions , there was an increase in interleukin 1β ( IL-1β ) and interleukin 10 ( IL-10 ) in both groups , while tumour necrosis factor alpha ( TNF-α ) was stimulated only in the conventional training group . Conclusion : Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training . Both interventions were equally effective in improving muscle strength and quality of life Ghigiarelli , JJ , Nagle , EF , Gross , FL , Robertson , RJ , Irrgang , JJ , and Myslinski , T. The effects of a 7-wk heavy elastic b and and weight chain program on upper body strength and upper body power in a sample of Division 1-AA football players . J Strength Cond Res 23(3 ) : 756 - 764 , 2009-The purpose of this study was to explore the effects of a 7-week heavy elastic b and and weighted-chain program on maximum muscular strength and maximum power in the bench press exercise . Thirty-six ( n = 36 ) healthy men aged 18 - 30 years old , from the Robert Morris University football team , volunteered to participate in this study . During the first week , predicted 1 repetition maximum ( 1RM ) bench press and a 5RM speed bench press tests were conducted . Subjects were r and omly divided into 3 groups ( n = 12 ) : elastic b and ( EB ) , weighted chain ( WC ) , and traditional bench ( C ) . During weeks 2 - 8 of the study , subjects were required to follow the prescribed resistance training program . Mean and SD of the predicted 1RM bench press and 5RM speed bench press were computed . A two-factor ( method X time ) analysis was applied to identify significant differences between the training groups . Significance was set at α = 0.05 . Results indicated a significant time ( p < 0.05 ) but no group effect for both predicted 1RM ( kg ) and 5RM peak power tests ( watts ) . Although not significant , results did show greater nonsignificant improvements in the EB ( 848 - 883 W ) and WC groups ( 856 - 878 W ) vs. control ( 918 - 928 W ) when the 2 highest and greatest values were selected regarding peak power . The use of EB and WC in conjunction with a general offseason strength and conditioning program can increase overall maximum upper-body strength in a sample of Division 1-AA football players . These types of training modalities add a unique training style and more flexibility with respect to exercise prescription for athletes and strength practitioners The power output generated with different barbell loads and which resistance generated the maximum mechanical power output ( Pmax ) during explosive bench press-type throws ( BT ) in a smith machine device were investigated in power-trained athletes . Thirty-one rugby league players were tested for 1 repetition maximum ( 1RM ) free-weight bench press strength ( 1RM BP ) . Maximal power output was assessed by the Plyometric Power System during BT using resistances of 40 , 50 , 60 , 70 , and 80 kg ( BT P40 , BT P50 , BT P60 , BT P70 , and BT P80 ) . It was found that BT Pmax occurred with resistance of 70.1 ± 7.9 kg , representing 55 ± 5.3 % of 1RM BP of 129.7 ± 14.3 kg . The power output with all loads except the BT P70 were different from the BT Pmax . The BT P70 and BT P80 were not different from each other . Furthermore , the BT P60 and BT P80 were not different from each other . This suggests that although resistances of 55 % 1RM BP may maximize power output during explosive BT , loads in the range of 46–62 % also allow for high power outputs . Resistances of 31–45 % of 1RM BP result ed in significantly lower power outputs . Compared with previous research of BT in strength-trained athletes , the results of this investigation suggest that power-trained athletes may generate their Pmax at higher percentages of 1RM Colado , JC and Triplett , NT . Effects of a short-term resistance program using elastic b and s versus weight machines for sedentary middle-aged women . J Strength Cond Res 22(5 ) : 1441 - 1448 , 2008-This study was design ed to determine whether different effects on functional capacity and body composition were produced by using different devices ( elastic b and s ( EBs ) versus weight machines ( WMs ) ) with the same resistance training program . Forty-five healthy sedentary middle-aged women volunteers were chosen and r and omly assigned to 1 of 3 groups : 21 subjects trained using EBs ( EBG ) , 14 in trained using WMs ( WMG ) , and 10 were controls ( CG ) . Both exercise groups trained with a periodized muscular endurance program twice a week for 10 weeks , with a total of 6 exercises per session for the major muscle groups . Exercise intensity was equalized by jointly monitoring the same targeted number of repetitions ( TNRs ) and rate of perceived exertion in active muscles ( RPE-AM ) . Functional capacity was assessed by using knee push-up ( KPU ) and 60-second squat ( S ) tests . Body composition was measured using an 8-polar bioelectrical impedance analyzer . The results for both the EBG and WMG show a decrease in fat mass ( p = 0.05 and p < 0.01 , respectively ) and an increase in both the fat-free mass ( p < 0.05 and p < 0.01 , respectively ) and the number of repetitions in the KPU ( p < 0.05 and p < 0.01 , respectively ) and S tests ( p < 0.01 in both ) . None of the variables measured for the CG varied significantly . It can be concluded that , independently of the device used , the combined monitoring of TNRs and RPE-AM can be a valid tool for controlling the resistance exercise intensity and can lead to healthy adaptations . EBs can thus offer significant physiological benefits that are comparable to those obtained from WMs in the early phase of strength training of sedentary middle-aged women Background High-intensity resistance training plays an essential role in the prevention and rehabilitation of musculoskeletal injuries and disorders . Although resistance exercises with heavy weights yield high levels of muscle activation , the efficacy of more user-friendly forms of exercise needs to be examined . Objective The aim of this study was to investigate muscle activation and perceived loading during upper-extremity resistance exercises with dumbbells compared with elastic tubing . Design A single-group , repeated- measures study design was used . Setting Exercise evaluation was conducted in a laboratory setting . Participants Sixteen female workers ( aged 26–55 years ) without serious musculoskeletal diseases and with a mean neck and shoulder pain intensity of 7.8 on a 100-mm visual analog scale participated in the study . Measurements Electromyographic ( EMG ) activity was measured in 5 selected muscles during the exercises of lateral raise , wrist extension , and shoulder external rotation during grade d loadings with dumbbells ( 2–7.5 kg ) and elastic tubing ( Thera-B and , red to silver resistance ) . The order of exercises and loadings was r and omized for each individual . Electromyographic amplitude was normalized to the absolute maximum EMG amplitude obtained during maximal voluntary isometric contraction and exercise testing . Immediately after each set of exercise , the Borg CR10 scale was used to rate perceived loading during the exercise . Results Resistance exercise with dumbbells as well as elastic tubing showed increasing EMG amplitude and perceived loading with increasing resistance . At the individually maximal level of resistance for each exercise — defined as the 3 repetitions maximum — normalized EMG activity of the prime muscles was not significantly different between dumbbells ( 59%–87 % ) and elastic tubing ( 64%–86 % ) . Perceived loading was moderately to very strongly related to normalized EMG activity ( r=.59–.92 ) . Limitations The results of this study apply only for exercises performed in a controlled manner ( ie , without sudden jerks or high acceleration ) . Conclusions Comparably high levels of muscle activation were obtained during resistance exercises with dumbbells and elastic tubing , indicating that therapists can choose either type in clinical practice . The Borg CR10 can be a useful aid in estimating intensity of individual rehabilitation protocol OBJECTIVE The aim of this study was to evaluate the efficacy and feasibility of two school-based RT programs to improve muscular fitness and body composition in adolescents . METHODS The study was conducted in Australia from July 2008 to June 2009 . Participants [ n=108 , mean age (SD)=15.0 ( 0.7 ) years ] were r and omized to free weights ( n=37 ) or elastic tubing ( n=41 ) RT groups and a control group was recruited ( n=30 ) . Participants in the RT groups completed 2 sets of 10 - 12 repetitions on 10 exercises for 8 weeks . Waist circumference , body composition ( bioelectrical impedance analysis ) and muscular strength ( bench press and leg press ) were assessed at baseline and posttest . RESULTS Boys ( p<0.001 ) and girls ( p<0.01 ) in both RT groups improved their body composition over the study period . Boys in both RT groups significantly improved both upper and lower body strength and their improvements were significantly greater than changes observed in the control group . Girls in the free weights groups achieved larger improvements in lower body strength compared to the control group ( p<0.05 ) . CONCLUSIONS Free weights and elastic tubing RT are feasible and effective strategies for improving aspects of health-related fitness in adolescents Objective The aim of this study was to evaluate muscle activity during hamstring rehabilitation exercises performed in training machine compared with elastic resistance . Design Six women and 13 men aged 28–67 yrs participated in a crossover study . Electromyographic ( EMG ) activity was recorded in the biceps femoris and the semitendinosus during the concentric and the eccentric phase of hamstring curls performed with TheraB and elastic tubing and Technogym training machines and normalized to maximal voluntary isometric contraction – EMG ( normalized EMG ) . Knee joint angle was measured using electronic inclinometers . Results Training machines and elastic resistance showed similar high levels of muscle activity ( biceps femoris and semitendinosus peak normalized EMG > 80 % ) . EMG during the concentric phase was higher than during the eccentric phase regardless of exercise and muscle . However , compared with machine exercise , slightly lower ( P < 0.05 ) normalized EMG values were observed using elastic resistance at 30- to 50-degree knee joint angle for the semitendinosus and the biceps femoris during the concentric and the eccentric phase , respectively . Perceived loading ( Borg CR10 ) was significantly higher ( P < 0.001 ) during hamstring curl performed with elastic resistance ( 7.58 ± 0.08 ) compared with hamstring curl performed in a machine ( 5.92 ± 0.03 ) . Conclusions Hamstring rehabilitation exercise performed with elastic resistance induces similar peak hamstring muscle activity but slightly lower EMG values at more extended knee angles and with higher perceived loading as hamstring curls using training machines Abstract Calatayud , J , Borreani , S , Colado , JC , Martin , F , Tella , V , and And ersen , LL . Bench press and push-up at comparable levels of muscle activity results in similar strength gains . J Strength Cond Res 29(1 ) : 246–253 , 2015—Electromyography ( EMG ) exercise evaluation is commonly used to measure the intensity of muscle contraction . Although research ers assume that biomechanically comparable resistance exercises with similar high EMG levels will produce similar strength gains over the long term , no studies have actually corroborated this hypothesis . This study evaluated EMG levels during 6 repetition maximum ( 6RM ) bench press and push-up , and subsequently performed a 5-week training period where subjects were r and omly divided into 3 groups ( i.e. , 6RM bench press group , 6RM elastic b and push-up group , or control group ) to evaluate muscle strength gains . Thirty university students with advanced resistance training experience participated in the 2-part study . During the training period , exercises were performed using the same loads and variables that were used during the EMG data collection . At baseline , EMG amplitude showed no significant difference between 6RM bench press and b and push-up . Significant differences among the groups were found for percent change ( & Dgr ; ) between pretest and posttest for 6RM ( p = 0.017 ) and for 1 repetition maximum ( 1RM ) ( p < 0.001 ) . Six repetition maximum bench press group and 6RM elastic b and push-up group improved their 1RM and 6RM ( & Dgr ; ranging from 13.65 to 22.21 ) tests significantly with similar gains , whereas control group remains unchanged . Thus , when the EMG values are comparable and the same conditions are reproduced , the aforementioned exercises can provide similar muscle strength gains |
467 | 24,277,633 | There was no benefit to administering antibiotics before the insertion of long-term CVCs to prevent Gram positive catheter-related infections .
Flushing or locking long-term CVCs with a combined antibiotic and heparin solution appeared to reduce Gram positive catheter-related sepsis experienced in people at risk of neutropenia through chemotherapy or disease .
Due to insufficient data it was not clear whether this applied equally to TCVCs and totally implanted devices ( TIDs ) , or equally to adults and children . | BACKGROUND This is an up date d version of the review which was first published in the Cochrane Data base of Systematic Review s in 2006 .
Long-term central venous catheters ( CVCs ) , including tunnelled CVCs ( TCVCs ) and totally implanted devices or ports ( TIDs ) , are increasingly used when treating oncology patients .
Despite international guidelines on sterile insertion and appropriate CVC maintenance and use , infection remains a common complication .
These infections are mainly caused by Gram positive bacteria .
Antimicrobial prevention strategies aim ed at these micro-organisms could potentially decrease the majority of CVC infections .
The aim of this review was to evaluate the efficacy of antibiotics in the prevention of Gram positive infections in long-term CVCs .
OBJECTIVES To determine the efficacy of administering antibiotics prior to the insertion of long-term CVCs , or flushing or locking long-term CVCs with a combined antibiotic and heparin solution , or both , to prevent Gram positive catheter-related infections in adults and children receiving treatment for cancer . | ABSTRACT The aim of the present study was to determine the efficacy of an antibiotic-lock technique in preventing endoluminal catheter-related infection with gram-positive bacteria in neutropenic patients with hematologic malignancies . Patients with nontunneled , multilumen central venous catheters were assigned in a r and omized , double-blinded manner to receive either 10 U of heparin per ml ( 57 patients ) or 10 U of heparin per ml and 25 μg of vancomycin per ml ( 60 patients ) , which were instilled in the catheter lumen and which were allowed to dwell in the catheter lumen for 1 h every 2 days . Insertion-site and hub swabs were taken twice weekly . The primary and secondary end points of the trial were significant colonization of the catheter hub and catheter-related bacteremia , respectively . Significant colonization of the catheter hub occurred in nine ( 15.8 % ) patients receiving heparin ( seven patients were colonized with Staphylococcus epidermidis , one patient was colonized with Staphylococcus capitis , and one patient was colonized withCorynebacterium sp. ) , whereas the catheter hubs of none of the patients receiving heparin and vancomycin were colonized ( P = 0.001 ) . Catheter-related bacteremia developed in four ( 7 % ) patients receiving heparin ( three patients had S. epidermidis bacteremia and one patient had S. capitisbacteremia ) , whereas none of the patients in the heparin and vancomycin group had catheter-related bacteremia ( P = 0.05 ) . The times to catheter hub colonization and to catheter-related bacteremia by the Kaplan-Meier method were longer in patients receiving heparin and vancomycin than in patients receiving heparin alone ( P = 0.004 and P = 0.06 , respectively ) . Our study shows that a solution containing heparin and vancomycin administered by using an antibiotic-lock technique effectively prevents catheter hub colonization with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients with hematologic malignancy BACKGROUND We compared the rates of infection in external catheters ( ECs ) and totally implantable devices ( TIDs ) and the effect of timing of insertion in children with acute lymphoblastic leukemia ( ALL ) . PROCEDURE Central line data was collected on all children with ALL referred to the National Guard Hospital , Jeddah . Data was collected retrospectively from 1996 to September 1999 and prospect ively thereafter . Only ECs were inserted prior to 1999 subsequently TIDs were preferred . RESULTS One hundred forty eight children with ALL , mean age 5.1 years had 129 ECs and 70 TIDs inserted for a total of 41,382 catheter days . The overall rate of infective episodes ( infections/1,000 catheter days ) was 3.43 . Of the initial 148 lines 100 developed complications of which 76 ( 51 % ) were secondary to an infective episode . Only young age and treatment protocol were risk factors for first line infections ( P < 0.05 ) . There was weak evidence that ECs had an earlier time to infection compared to TIDs ( P = 0.056 ) . CONCLUSIONS In this study , population central lines were associated with a high rate of infection . Treatment protocol and age were the only significant risk factors when only first lines were considered . Delaying catheter insertion for more than 3 weeks from diagnosis did not reduce the risk of infection Objective .Critically ill neonates are at high risk for vascular catheter – related bloodstream infection ( CRBSI ) , most often caused by coagulase-negative staphylococci . Most CRBSIs with long-term devices derive from intraluminal contaminants . The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI . Methods .A prospect i ve , r and omized double-blind trial was conducted during 2000–2001 at a community hospital level III NICU . Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were r and omized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline ( n = 43 ) or heparinized saline that contained vancomycin 25 μg/mL ( n = 42 ) . The origin of each nosocomial bloodstream infection ( BSI ) was studied by culturing skin , catheter hubs , and implanted catheter segments and blood cultures , demonstrating concordance by restriction-fragment DNA subtyping . Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms . The main outcome measures were ( 1 ) CRBSIs and ( 2 ) colonization or infection by vancomycin-resistant Gram-positive bacteria . Results .Two ( 5 % ) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 ( 30 % ) of 43 in the control group ( 2.3 vs 17.8 per 1000 catheter days ; relative risk : 0.13 ; 95 % confidence interval : 0.01–0.57 ) . No vancomycin-resistant enterococci or staphylococci were recovered from any cultures . Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy . Twenty-six neonates ( 8 vancomycin-lock group , 18 control group ) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted . Conclusions .Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia . The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice In this prospect i ve cohort study , minocycline-ethylenediaminetetraacetate ( M-EDTA ) was used as a lock solution in indwelling ports inserted in 14 children with cancer . No port infections , thrombotic events , or other adverse events were observed , compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin . M-EDTA is a promising lock solution in long-term catheters The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter‐related infection in melanoma patients treated with interleukin‐2 ( IL‐2 ) plus interferon‐α and chemotherapy ( biochemotherapy ) OBJECTIVE To determine whether adding vancomycin to central venous catheter ( CVC ) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms . STUDY DESIGN Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were r and omly assigned to receive a heparin CVC flush solution ( n = 31 ) or a heparin-vancomycin CVC flush solution ( n = 32 ) . RESULTS During 9158 catheter days , 6.5 % of the patients in the heparin group and 15.6 % of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms ( p = 0.43 ) . The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group ( p = 0.25 ) . There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates . Streptococcus viridans infection was not attributable to luminal colonization . CONCLUSION The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms . Bacteremia with Streptococcus viridans was not related to the use of a CVC Taurolidine has demonstrated inhibition of biofilm formation in vitro . The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters . Forty‐eight children with cancer were r and omized to catheter locking by heparin ( n = 22 ) or taurolidine ( n = 26 ) , respectively . After removal , catheters were examined by st and ardized scanning electron microscopy to assess quantitative biofilm formation . Biofilm was present if morphologically typical structures and bacterial cells were identified . Quantitative and semi‐quantitative cultures were also performed . Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group . A positive culture was made of six of the catheters locked with taurolidine and heparin , respectively ( p = 0.78 ) . The rate of catheter‐related bloodstream infections ( CRBSI ) was 0.1 per 1000 catheter‐days using taurolidine and 0.9 per 1000 catheter‐days using heparin ( p = 0.03 ) . This r and omized trial confirmed that the use of taurolidine as catheter‐lock compared with heparin reduced the rate of CRBSIs ; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups Abstract : In all , 88 patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were r and omized to receive either one single bolus intravenous injection of teicoplanin , 400 mg , or no teicoplanin immediately before insertion of a double‐lumen Hickman catheter . Lower incidences of catheter‐related Gram‐positive sepsis were recorded in patients receiving prophylactic teicoplanin ; exit site infection , tunnel infection and catheter‐related Gram‐positive septicaemia were all reduced . The benefit of prophylactic teicoplanin was observed particularly among patients who were already neutropenic at the time of catheterization . All Gram‐positive organisms isolated from infected skin sites or from blood cultures taken from Hickman catheters were susceptible to teicoplanin . No adverse reaction was reported in any of the patients receiving prophylaxis . Prophylactic teicoplanin , therefore , may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy , to reduce the early incidence of catheter‐related sepsis , particularly during the period of neutropenia following chemotherapy Prospect ively since 11/1997 , all central venous catheter related bacteremias in our dialysis center ( n = 60 ) was recorded . We systematic ally tested antibiotic lock technique using pure heparin ( 1 ml = 5000 Ul ) mixed with antibiotic matched to isolated micro-organism after 15 days of systemic antibiotherapy . During 39 months of study , 27 bacteremias were documented from 23 patients . Seventeen locks in 15 patients were performed after each dialysis sessions during one month . Associated tunnel infection did not allow to stop the lock in 3 cases . In the 12 remaining patients , we observed 4 recurrences for 3 patients after the stop of the lock with the same micro-organism in 3 times/4 without modifications of antibiotics sensibility . No septic metastases were notified and the patency of all catheters were respected . The incidence of bacteremias was 4.6 per 1000 catheters days before the lock and 0.88 after , during a mean observation period of 15 months per patients . Sterilisation of infected catheters seems possible and the incidence of bacteremias is reduce by the lock technique without coming out of septic complications or selected micro-organisms Background Taurolidin/Citrate ( TauroLock ™ ) , a lock solution with broad spectrum antimicrobial activity , may prevent bloodstream infection ( BSI ) due to coagulase-negative staphylococci ( CoNS or ' MRSE ' in case of methicillin-resistant isolates ) in pediatric cancer patients with a long term central venous access device ( CVAD , Port- or/Broviac-/Hickman-catheter type ) . Methods In a single center prospect i ve 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 ( group 1 , heparin lock with 200 IU/ml sterile normal saline 0.9 % ; Canusal ® Wockhardt UK Ltd , Wrexham , Wales ) and all patients from April 2005 to March 2007 ( group 2 ; taurolidine 1.35%/Sodium Citrate 4 % ; TauroLock ™ , Tauropharm , Waldbüttelbrunn , Germany ) . Results In group 1 ( heparin ) , 90 patients had 98 CVAD in use during the surveillance period . 14 of 30 ( 47 % ) BSI were ' primary Gram positive BSI due to CoNS ( n = 4 ) or MRSE ( n = 10 ) ' [ incidence density ( ID ) ; 2.30 per 1000 inpatient CVAD-utilization days].In group 2 ( TauroLock ™ ) , 89 patients had 95 CVAD in use during the surveillance period . 3 of 25 ( 12 % ) BSI were caused by CoNS . ( ID , 0.45 ) . The difference in the ID between the two groups was statistically significant ( P = 0.004 ) . Conclusion The use of Taurolidin/Citrate ( TauroLock ™ ) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients Cancer patients with long-term venous catheter are at risk for thromboembolic complications at the catheter tip and in the adjacent venous vessels . We assessed whether local thrombogenicity could be prevented with an experimental coated ( with athrombogenic layer ) catheter device ( CD ) compared to an uncoated CD . Patients requiring a long-term venous catheter were r and omly allocated to receive either a st and ard uncoated or experimental coated ( with athrombogenic Camouflage ® layer ) CD . The athrombogenic layer creates a barrier against non-specific adsorption of plasma proteins . The primary endpoint was urokinase injection in cases of an unsuccessful blood aspiration from the CD . Secondary endpoints included early ( haematoma , pneumothorax ) and late ( venous thrombosis , infection ) catheter-associated complications and catheter defects . One hundred and seventy-nine patients were r and omly assigned to a CD ( experimental n = 89/st and ard n = 90 ) . One hundred and ten ( 62 % ) patients with a total of 1,286 catheter taps were analysed for the primary endpoint . Necessity for urokinase injection was 8/680 ( 1.2 % experimental ) vs. 33/606 ( 5.4 % st and ard ) per catheter tap and 4/55 ( 7.3 % experimental ) vs. 18/55 ( 32.7 % st and ard ) per patient . A repeated measures logistic regression to assess the effect of coating yielded an odds ratio of 3.5 ( 95 % confidence interval , 1.2–10.4 ; p = 0.03 ) for the primary endpoint . All patients allocated per protocol were analysed for the secondary endpoints . Nine ( 5.4 % ) local thrombotic complications , seven ( 4.1 % ) catheter infections , and no catheter defect were observed . Athrombogenic coating of CD in cancer patients result ed in a significant reduced necessity for urokinase injections and subsequently less inconvenience for patients and fewer costly interventions We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms ( VSO ) in cancer patients with a tunneled central venous catheter ( CVC ) . Eighty-three patients who had a single lumen CVC were r and omized to use a heparin solution ( 25 U/ml ) for daily catheter flush with ( HepVan ) or without ( Hep ) vancomycin , 25 mcg/ml . Febrile episodes were recorded , and central and peripheral blood cultures were drawn before beginning antibiotic therapy . Patients participated in follow-up to 16,677 catheter days ( 8,666 Hep and 8,011 HepVan ) , and 143 febrile episodes were recorded ( 82 Hep and 61 HepVan ) . Forty-four episodes of bacteremia occurred , 23 of them due to VSO ( 16 occurred in the Hep group and 7 in the HepVan group ( P = 0.19 ) . VSO bacteremia occurred in 14 neutropenic ( absolute neutrophil count < 500 x 10(9)/l ) episodes ( 7 Hep vs. 7 HepVan ) and in 9 non-neutropenic episodes ( 9 Hep vs. O HepVan ; P = 0.013 ) . Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients , supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients Since 1984 , 316 subcutaneous ports ( SP ) and 339 external venous catheters ( EC ) [ Roko Catheter , The Hospital for Sick Children ( HSC ) ] have been inserted in hematology/ oncology patients at HSC . During a 22-month period ( July 1987 to April 1989 ) , a committed central line nurse ( J.I. ) prospect ively collected clinical and microbiologic data on 144 consecutive SPs and 130 consecutive ECs . Children with the SP had 0.6 infected lines and 0.7 infectious episodes per 1,000 patient days compared to 2.9 infected lines and 4.3 infectious episodes per 1,000 patient days with the EC ( p < 0.001 ) . This lower infectious complication rate with SP was demonstrated in the entire group of unselected patients and in a cohort of children with acute lymphoblastic leukemia ( ALL ) receiving intensive chemotherapy , and it was evident in all age groups . In view of the other advantages of SP – normal activity , absence of the need for home maintenance , improved body image , less expense – these data suggest that SPs are the preferred device in pediatric patients and provide effective venous access with acceptable complication rates Abstract A prospect i ve , r and omized , open study comparing two doses of teicoplanin with no therapy administered at the time of insertion of a central venous catheter was performed in patients with hematological malignancies and in patients scheduled to undergo allogeneic or autologous stem cell transplantation . The study was design ed as a group sequential study . At predetermined intervals statistical analysis was performed for the main efficacy variable , which was the number of days to treatment failure . Sixty-five patients were r and omized . Three patients were judged to be not evaluable . Baseline characteristics were identical in the two groups . No differences were found in overall infections , bacteremias , gram-positive infections , or local infections between the teicoplanin and control groups . Teicoplanin given at the time of insertion of central venous catheters did not reduce the risk of bacteremias or other line-associated infections Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection . The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters ( CVCs ) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia . Proven CVC-related bloodstream infection ( BSI ) was defined as the isolation of the same species from peripheral blood culture and CVC tip ( Maki technique ) . This r and omized , prospect i ve clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC ( n=51 ) to a control arm using a st and ard uncoated triple-lumen CVC ( n=55 ) . Patients were treated for acute leukemia ( n=89 ) , non-Hodgkin ’s lymphoma ( n=10 ) , and multiple myeloma ( n=7 ) . Study groups were balanced regarding to age , sex , underlying diseases , insertion site , and duration of neutropenia . The CVCs were in situ a mean of 14.3±8.2 days ( mean±SD ) in the study group versus 16.6±9.7 days in the control arm . Catheter-related colonization was observed less frequently in the study group ( five vs nine patients ; p=0.035 ) . CVC-related BSI were significantly less frequent in the study group ( one vs eight patients ; p=0.02 ) . In summary , in patients with severe neutropenia , CH-SS-impregnated CVCs yield a significant antibacterial effect result ing in a significantly lower rate of catheter-related colonization as well as CVC-related BSI To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis ( CRS ) in immunocompromised patients , 98 cancer patients were entered into a r and omized placebo-controlled trial . Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation ( group A ) or required chemotherapy for a solid tumour ( group B ) . Eligible patients were r and omized to receive either 500 mg vancomycin in 250 ml of 0.9 % saline prior to catheter insertion followed by a further 500 mg infused via the established catheter , or the same regimen with 0.9 % saline alone . In group A , there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters ( 57 % ) . Six catheters were removed because of CRS . No significant difference was found in the incidence of CRS between the two arms . Of the 37 evaluable catheters in group B , CRS occurred in 6 ( 16 % ) , and none of the catheters required removal because of CRS . Again , no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo . These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease Exit-site and tunnel infections of tunnelled central intravascular catheters are a frequent source of morbidity among neutropenic patients and may necessitate catheter removal . They require antimicrobial therapy that increases healthcare costs and is associated with adverse drug reactions . A prospect i ve r and omized clinical trial was conducted among adult patients undergoing chemotherapy in a haematology unit . Tunnelled intravascular catheters were r and omized to receive the control of a st and ard dressing regimen as recommended by the British Committee for St and ards in Haematology , or to receive the intervention of a sustained-release chlorhexidine dressing . Follow-up data were available in 112 of 114 tunnelled intravascular catheters which were r and omized . Exit-site or combined exit-site/tunnel infections occurred in 23 ( 43 % ) of 54 catheters in the control group , and five ( 9 % ) of 58 catheters in the intervention group [ odds ratio ( OR ) for intervention group compared with control group = 0.13 , 95 % confidence intervals ( CI ) 0.04 - 0.37 , P<0.001 ] . More tunnelled intravascular catheters were prematurely removed from the control group than the intervention group for documented infections [ 20/54 ( 37 % ) vs 6/58 ( 10 % ) , OR=0.20 , 95%CI 0.53 - 0.07 ] . However , there was no difference in the numbers of tunnelled intravascular catheters removed for all proven and suspected intravascular catheter-related infections [ 21/54 ( 39 % ) vs 19/58 ( 33 % ) ] , or in the time to removal of catheters for any reason other than death or end of treatment for underlying disease . Thus chlorhexidine dressings reduced the incidence of exit-site/tunnel infections of indwelling tunnelled intravascular catheters without prolonging catheter survival in neutropenic patients , and could be considered as part of the routine management of indwelling tunnelled intravascular catheters among neutropenic patients Forty-five children with oncologic or hematologic disorders requiring tunneled central venous catheters ( TCVC ) for the administration of immunosuppressive therapy were r and omized to receive either 10 U/mL heparin ( H ) ( 24 patients ) or a solution of 10 U/mL H and 25 micrograms/mL vancomycin ( H-V ) ( 21 patients ) for all catheter flushes . Episodes of fever or suspected sepsis were evaluated to determine whether the addition of vancomycin to the flush solution would alter the incidence of symptomatic bacteremia attributed to luminal colonization of TCVC with vancomycin-susceptible bacteria . Patients were enrolled for 247 + /- 150 days , accounting for a total of 11,095 days of catheter use . Bacteremia attributed to luminal colonization with vancomycin-susceptible organisms occurred in five patients ( six infections ) receiving H alone compared with zero patients receiving H-V ( P = .035 ) . The time to the first episode of bacteremia with vancomycin-susceptible organisms , analyzed by Kaplan-Meier survival curves , was significantly longer in patients receiving H-V ( P = .04 ) . There were no differences in the incidence of other infections including bacteremia attributed to luminal colonization with vancomycin-resistant organisms , other bacteremias ( including those arising from the catheter exit site ) , exit-site cellulitis , or fungal infections . No organisms resistant to vancomycin were identified . Vancomycin could not be detected in the peripheral blood of patients receiving vancomycin in the flush solution . No vancomycin-related toxicities were noted . We conclude that the use of an H-V flush solution in immunocompromised patients with TCVC can decrease the frequency of bacteremia attributed to luminal colonization with vancomycin-susceptible bacteria Objective This study was performed to evaluate the effect of a silver-impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters . Summary Background Data Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients . Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection . Methods The authors prospect ively r and omized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff . All patients then were followed prospect ively for infectious morbidity until the device was removed or the patient died . Results The hazard rate for infection/day ( 95 % confidence limits ) was 0.0022 ( 0.0015 to 0.0030 ) for st and ard catheters compared with 0.0027 ( 0.0019 to 0.0037 ) for catheters with silver-impregnated cuffs ( p = not significant ) . Regression analysis of infection-free Interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion . Conclusions The study indicated no effect of a silver-impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias , tunnel infections , or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters Infections associated with double-lumen central venous catheters ( CVCs ) in patients undergoing BMT are presented . We prospect ively studied infections occurring with 46 CVCs in 40 patients with malignancies during and up to 30 days after BMT . We r and omised patients with insertions of CVCs to receive either a short course of vancomycin 500 mg x 3 peri-operatively ( 16 CVCs ) or no VCM ( 11 CVCs ) . Six per cent of CVCs in the group with vancomycin prophylaxis became infected with Gram positive microorganisms compared with 55 % in the control group ( P < 0.05 ) . Next , 19 patients with CVCs were all given prophylaxis , so finally 35 patients were given vancomycin compared with 11 patients with no vancomycin . In a total of 11 CVC-related infections , 79 % of the microbiological isolates were staphylococci , all of which were sensitive to vancomycin . Vancomycin prophylaxis reduced the number of infected CVCs to 11 % compared with 45 % ( P < 0.05 ) and bacteraemias to 6 % compared with 45 % ( P < 0.01 ) . All infections responded to antibiotic treatment . Prophylactic short- duration vancomycin during insertion of CVCs may reduce the incidence of line-associated infections and Gram positive bacteraemias in patients undergoing BMT PURPOSE To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure . METHODS Between May 2000 and March 2002 , 66 patients were r and omly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were r and omly assigned to receive an unimpregnated catheter . Patients were followed prospect ively until the catheter was removed . Catheter-related infection was determined through quantitative catheter cultures , quantitative blood cultures , or both . RESULTS Both groups of patients were similar in age , sex , underlying disease , type of dialysis ( continuous vs. intermittent ) , neutropenia during catheterization and its duration , catheter insertion difficulties , and administration of blood products or medication . The mean ( + /- SD ) catheter dwell time was the same in both groups ( 8 + /- 6 days , P = 0.7 ) . There were seven catheter-related infections ( 11 % ) , all associated with the use of unimpregnated catheters . Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection ( P = 0.006 ) . CONCLUSION The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer , we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter " flush solution . " In a prospect i ve , placebo-controlled , double-blinded , r and omized trial , 69 children with different types of malignancies were studied . The central venous catheters in these children were flushed with either the st and ard solution ( normal saline + 100 U/ml of heparin ) or the study solution ( 25 microgram/ml of both amikacin and vancomycin added to the st and ard solution ) . At the conclusion of the study , 64 children with a total of 67 indwelling central venous lines were assessable . The total catheter days on study were 20,700 days , with a median of 323 catheter days per patient . We documented 10 events of catheter-related infections ( 0.49 events/1,000 catheter days at risk ) . Five of these events were catheter-related sepsis ( 0.24 sepses/1,000 catheter days ) : two were fungal and three were bacterial . Due to the low incidence of catheter-related sepsis in this study , no statement regarding the prophylactic use of antibiotics could be made . The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in h and ling these catheters . Staff education is essential , and probably the most effective factor in preventing catheter-related sepsis PURPOSE Infection is a serious complication of central venous catheters in immunocompromised patients . Catheter-related infection may be caused by fibrin deposition associated with catheters . Interventions design ed to decrease fibrin deposition have the potential to reduce catheter-related infections . The purpose of this study was to evaluate the role of low-dose unfractionated heparin in preventing catheter-related bloodstream infection in patients with hemato-oncological disease . PATIENTS AND METHODS This study was a r and omized , controlled trial in which patients with nontunneled catheters were r and omly assigned to receive either intravenous unfractionated heparin ( continuous infusion of 100 U/kg per day ) or 50 mL/day of normal saline solution as a continuous infusion ( control group ) . Heparin was continued until the day of discharge . Catheter-related bloodstream infection was defined according to Infectious Disease Society of America guidelines . RESULTS Two hundred and eight patients were r and omly assigned . Four patients were excluded after assignment . Ultimately , 204 patients were analyzed . Catheter-related bloodstream infection occurred in 6.8 % ( 7 of 102 catheters ) of those in the heparin group ( 2.5 events per 1,000 days ) and in 16.6 % ( 17 of 102 catheters ) of those in the control group ( 6.4 events per 1,000 days ) ( P = .03 ) . No other risk factors were found for the development of catheter-related bloodstream infection . Four and five patients experienced severe bleeding in the heparin and control groups , respectively ( P = .2 ) . We did not observe heparin-induced thrombocytopenia . CONCLUSION The use of continuous infusion of low-dose unfractionated heparin ( 100 U/kg per day ) can be a practical and economical approach to the prevention of catheter-related bloodstream infection in patients with hemato-oncological disease Background : Contamination of central catheters is frequent , and biofilm perpetuates infections . Heparin does not protect against infections because it has no antibiotic action . Minocycline and edetic acid ( M-EDTA ) , a potent calcium chelating agent that destroys bacterial and fungal cell membrane and disrupts biofilm , may be an alternative to allow the associated antibiotic to act locally at a high and safe concentration . Methods : Fifty children with cancer and a port-a-cath were followed up : 26 received heparin ( group 1 ) and 24 M-EDTA ( group 2 ) . A total of 762 serial prospect i ve blood cultures were obtained , 387 from group 1 and 375 from group 2 . Results : In group 1 ( heparin ) , 19 blood cultures were positive , and infection incidence was 73.1 % ( 19/26 ports ) . In group 2 ( M-EDTA ) , 5 blood cultures were positive , and the incidence rate was 20.8 % ( 5/24 ports ) . Conclusion : M-EDTA , compared with heparin , prevents and treats catheter infections , and is a promising alternative to decrease sepsis during chemotherapy UNLABELLED Antimicrobial central venous catheters are discussed as a device to reduce catheter-related infections . Previously we have reported a study with 223 adult surgical patients r and omized to receive either a rifampicin-miconazole-loaded central venous catheter ( CVC ) ( n=118 ) or a st and ard CVC ( n=105 ) . The antimicrobial CVC was shown to reduce catheter colonization ( CC ) and catheter-related local infection ( CRI ) significantly even at long-term catheterization . Here , we present further evaluation of the study focusing on possible benefits for high-risk patients . Subgroup analyses showed a pronounced reduction of CC and CRI in male , overweight and oncology patients . Important covariates were skin colonization for CC and oncological disease for CRI . Odds ratio ( OR ) for reducing CC was 0.076 ( 95 % CI : 0.016 - 0.360 ) and CRI was reduced from 26 % to 2.3 % ( p=0.001 ) in the cancer subgroup . Ex vivo long-term antimicrobial activity of modified catheters exceeded 4 weeks . CONCLUSION Immunocompromized patients suffering from cancer , transplantation , and dialysis patients with a long-term vascular access may mostly benefit from rifampicin-miconazole-releasing catheters BACKGROUND A catheter lock solution containing 1.35 % taurolidine and 4 % citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds . AIM To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter ( CVC ) lock solutions in paediatric patients with haematological malignancies . METHODS Seventy-one patients aged 1.4 - 18 years were r and omized to two treatment groups using either heparin ( N = 36 ) or taurolidine citrate ( N = 35 ) . Infectious complications and clinical side-effects were prospect ively monitored and microbial colonization of catheters was assessed at the time of removal . FINDINGS There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group ( 0.3 vs 1.3 infections per 1000 catheter-days ; P = 0.03 ) . Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups . Microbial colonization was found in 25.4 % catheters . The time of no-lock use , but not the type of lock solution or time of observation , was a significant predictor of catheter colonization ( P = 0.004 ) . Colonization was not observed in CVCs used immediately with taurolidine citrate lock . Seven patients in the taurolidine citrate group ( 20 % ) experienced side-effects ( nausea , vomiting , abnormal taste sensations ) . CONCLUSION The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients . Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion , but not after a period of no-lock catheter use BACKGROUND To determine if the catheter lock taurolidine can reduce the number of catheter-related bloodstream infections ( CRBSI ) in pediatric cancer patients with tunneled central venous catheters ( CVC ) . PROCEDURE During a study period of 34 months , 129 newly placed tunneled CVCs in 112 patients were r and omly assigned to st and ard lock with heparin solution or experimental lock with a taurolidine solution ( Clinical Trials.gov Identifier NCT00735813 ) . RESULTS Sixty-five CVCs were included in the st and ard group and 64 CVCs in the experimental group . The groups were comparable regarding patients ' characteristics . A total number of 72 bloodstream infections of which 33 were CRBSIs were observed during 39,127 CVC-days . A lower rate of CRBSI ( 0.4 per 1,000 CVC-days ) was observed in the experimental arm compared with the st and ard arm ( 1.4 per 1,000 CVC-days , incidence rate ratio ( IRR ) = 0.26 ; 95 % confidence interval ( CI ) 0.09 - 0.61 ; P = 0.001 ) . A lower rate of total bloodstream infections ( 1.2 per 1,000 CVC-days ) was also observed in the experimental arm compared with the st and ard arm ( 2.5 per 1,000 CVC-days , IRR = 0.49 ; 95 % CI 0.29 - 0.82 ; P = 0.004 ) . Median interval from catheter insertion until first CRBSI was significantly lower in the st and ard group ( 156 days , range 12 - 602 ) compared with the experimental group ( 300 days , range 12 - 1,176 ; P = 0.02 ) . Premature removal of the CVC due to infection and overall CVC survival were similar in the two study groups . CONCLUSION Locking of long-term tunneled CVC with taurolidine significantly reduces catheter-related bloodstream infections in children with cancer PURPOSE To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin ( M-R ) in reducing catheter-related bloodstream infections . PATIENTS AND METHODS This prospect i ve , r and omized , double-blind clinical trial was conducted at M.D. And erson Cancer Center , a tertiary care hospital in Houston , TX . All patients in the trial had a malignancy . RESULTS Between September 1999 and May 2002 , 356 assessable catheters were used : 182 M-R and 174 nonimpregnated . The patients ' characteristics were comparable between the two study groups . The mean ( + /- st and ard deviation ) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters ( 66.21 + /- 30.88 v 63.01 + /- 30.80 days ) . A total of 17 catheter-related bloodstream infections occurred during the course of the study . Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters , with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days , respectively ( P = .003 ) . Gram-positive cocci accounted for the majority of the organisms causing the infections . There were no allergic reactions associated with M-R catheters . CONCLUSION Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients PURPOSE To develop an evidence -based guideline on central venous catheter ( CVC ) care for patients with cancer that addresses catheter type , insertion site , and placement as well as prophylaxis and management of both catheter-related infection and thrombosis . METHODS A systematic search of MEDLINE and the Cochrane Library ( 1980 to July 2012 ) identified relevant articles published in English . RESULTS The overall quality of the r and omized controlled trial evidence was rated as good . There is consistency among meta-analyses and guidelines compiled by other groups as well . RECOMMENDATIONS There is insufficient evidence to recommend one CVC type or insertion site ; femoral catheterization should be avoided . CVC should be placed by well-trained providers , and the use of a CVC clinical care bundle is recommended . The use of antimicrobial/antiseptic-impregnated and /or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs , particularly in high-risk groups ; more research is needed . The prophylactic use of systemic antibiotics is not recommended before insertion . Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy ; more research is needed . Before starting antibiotic therapy , cultures should be obtained . Some life-threatening infections require immediate catheter removal , but most can be treated with antimicrobial therapy while the CVC remains in place . Routine flushing with saline is recommended . Prophylactic use of warfarin or low-molecular weight heparin is not recommended , although a tissue plasminogen activator ( t-PA ) is recommended to restore patency to occluded catheters . CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy BACKGROUND Catheter-related bloodstream infections ( CR-BSIs ) are associated with substantial mortality , prolongation of hospital stay , and increased cost of care . Dalbavancin , a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen , possesses excellent activity against clinical ly important gram-positive bacteria , suggesting utility in the treatment of patients with CR-BSIs . METHODS A phase 2 , open-label , r and omized , controlled , multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin , administered as a single 1000-mg dose followed by a 500-mg dose 1 week later , with intravenous vancomycin , administered twice daily for 14 days . Gram-positive bacteria isolated in this study included coagulase-negative staphylococci ( CoNS ) and Staphylococcus aureus , including methicillin-resistant S. aureus ( MRSA ) . RESULTS Infected patients who received weekly dalbavancin ( n=33 ) had an overall success rate ( 87.0 % ; 95 % confidence interval [ CI ] , 73.2%-100.0 % ) that was significantly higher than that of those who received vancomycin ( n=34 ) ( 50.0 % ; 95 % CI , 31.5%-68.5 % ) . Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs . CONCLUSIONS Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus , including MRSA PURPOSE To determine whether an antibiotic flush solution containing vancomycin , heparin , and ciprofloxacin ( VHC ) can prevent the majority of line infections . PATIENTS AND METHODS A prospect i ve double-blind study was performed comparing VHC to vancomycin and heparin ( VH ) to heparin alone in 126 pediatric oncology patients . RESULTS The 153 assessable lines result ed in 36,944 line days studied . There were 58 blood stream infections ( 43 gram-positive , 14 gram-negative , and one fungal ) . Forty were defined as line infections ( 31 heparin , three VH , six VHC ) . The time to develop a line infection was significantly increased using either antibiotic flush ( VH , P = .011 ; VHC , P = .036 ) . The rate of total line infections ( VH , P = .004 ; VHC , P = .005 ) , gram-positive line infections ( VH , P = . 028 ; VHC , P = .022 ) , and gram-negative line infections ( VH , P = .006 ; VHC , P = .003 ) was significantly reduced by either VH or VHC . Sixty-two ( 41 % ) of the lines developed 119 occlusion episodes ( heparin , 3.99 per 1,000 line days ; VHC , 1.75 per 1,000 line days ; P = .0005 ) . Neither antibiotic could be detected after flushing , and no adverse events were detected , including increased incidence of vancomycin-resistant Enterococcus colonization or disease . CONCLUSION The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care re sources BACKGROUND Antibiotic prophylaxis during placement of implanted central venous access ports ( CVAP ) has not been studied . This retrospective review compared the rate of catheter-related infections ( CRIs ) with and without perioperative antibiotics . METHODS This was a single-center study that compared patients treated with and without a single dose of antibiotics during CVAP placement . CRIs were defined as a patient treated with antibiotics for port site in duration , positive blood cultures , or suspicion of infection that led to port removal within 30 days of placement . RESULTS CVAP were placed in 459 patients , 103 of whom ( 22.4 % ) received antibiotic prophylaxis . Surgical technique and patient demographics were similar to those patients not receiving antibiotics ( 356 ) . All 9 ( 2 % ) CRIs occurred in the non-prophylactic antibiotic group ( P = .218 ) , with 5 infections result ing in port removal . CONCLUSIONS Single-dose perioperative antibiotics may decrease CVAP infection rates and should be studied further in a prospect i ve r and omized trial |
468 | 24,590,693 | Overall , there remains insufficient evidence to conclude that any intervention may increase or decrease trust in doctors .
This may be due in part to the sensitivity of trust instruments , and a ceiling effect , as trust in doctors is generally high . | BACKGROUND Trust is a fundamental component of the patient-doctor relationship and is associated with increased satisfaction , adherence to treatment , and continuity of care .
Our 2006 review found little evidence that interventions improve patients ' trust in their doctor ; therefore an up date d search was required to find out if there is further evidence of the effects of interventions that may improve trust in doctors or groups of doctors .
OBJECTIVES To up date our earlier review assessing the effects of interventions intended to improve patients ' trust in doctors or a group of doctors . | PURPOSE this study was conducted to evaluate the feasibility and acceptability of a managed-care approach ( group visits ) on delivering care to uninsured or inadequately insured patients with type 2 diabetes . METHODS One hundred twenty patients with uncontrolled type 2 diabetes were r and omly assigned to receive care in group visits or usual care for 6 months . At baseline , 3 months , and 6 months , the feasibility and acceptability of this model of healthcare delivery were assessed through the patients ' responses to the Primary Care Assessment Tool and the Trust in Physician Scale . Attendance records were kept for each group . RESULTS Patients who received care in group visits showed an improved sense of trust in their physician compared with patients who continued to receive usual care . There was a tendency for patients in groups to report better coordination of their care , better community orientation , and more culturally competent care . Patient attendance at the groups also indicated good acceptance of this form of healthcare delivery . CONCLUSIONS Group visits were feasible and acceptable to these uninsured and inadequately insured patients with uncontrolled type 2 diabetes and fostered an improved sense of trust in their physician PURPOSE The purpose of the study was to evaluate perceptions of care delivered through group visits to disadvantaged patients with type 2 diabetes . METHODS One hundred eighty-six patients with uncontrolled type 2 diabetes were r and omly assigned to receive care in group visits or usual care for 12 months . Their perceptions of the care they received were measured at baseline and 6 and 12 months by the Primary Care Assessment Tool ( PCAT ) , the Diabetes-Specific Locus of Control ( DLC ) survey , and the Trust in Physician Scale ( TPS ) . RESULTS Compared to patients in usual care , group visit patients ' PCAT scores were higher in the domains of ongoing care ( P = .001 ) , community orientation ( P < .0001 ) , and cultural competence ( P = .022 ) . In addition , group patients had higher scores for the Powerful-Other Health Professional subscale of the DLC survey ( P = .010 ) . CONCLUSIONS Patients assigned to group visits had generally more positive perceptions about their care in the areas of ongoing care , community orientation of care , and cultural competence of care than did those in usual care . The perception that one 's health professional is powerful , however , has been associated with a reluctance of patients to make medication changes on their own in previous studies . These findings suggest the need for modification in the way that group visits are conducted to empower and activate patients while still delivering continuous , culturally competent , and community-oriented care BACKGROUND Poor quality of information transfer about the benefits and risks of statin drug use may result in patients not making informed decisions that they can act on in a timely fashion . METHODS The effect of a decision aid about statin drugs on treatment decision making in 98 patients with diabetes was determined in a cluster r and omized trial of decision aid vs control pamphlet , with concealed allocation , blinding of participants to study goals , and adherence to the intention-to-treat principle . Twenty-one endocrinologists conducted specialty outpatient metabolic consultations . Patients in the intervention group received Statin Choice , a tailored decision aid that presents the estimated 10-year cardiovascular risk , the absolute risk reduction with use of statin drugs , and the disadvantages of using statin drugs . Patients in the control group received the institution 's pamphlet about cholesterol management . We measured acceptability , knowledge about options and cardiovascular risk , and decisional conflict immediately after the visit , and adherence to pill taking was measured 3 months later . RESULTS Patients favored using the decision aid ( odds ratio [ OR ] , 2.8 ; 95 % confidence interval [ CI ] , 1.2 - 6.9 ) ; patients who received the decision aid ( n = 52 ) knew more ( difference , 2.4 of 9 points ; 95 % CI , 1.5 - 3.3 ) , had better estimated cardiovascular risk ( OR , 22.4 ; 95 % CI , 5.9 - 85.6 ) and potential absolute risk reduction with statin drugs ( OR , 6.7 ; 95 % CI , 2.2 - 19.7 ) , and had less decisional conflict ( difference , -10.6 ; 95 % CI , -15.4 to -5.9 on a 100-point scale ) than did patients in the control group ( n = 46 ) . Of 33 patients in the intervention group taking statin drugs at 3 months , 2 reported missing 1 dose or more in the last week compared with 6 of 29 patients in the control group taking statin drugs ( OR , 3.4 ; 95 % CI , 1.5 - 7.5 ) . CONCLUSIONS A decision aid enhanced decision making about statin drugs and may have favorably affected drug adherence OBJECTIVE Assess use of and reactions to an interactive , tailored CD-ROM to enhance oncologist-patient communication . METHODS Participating oncologists ( n=48 ) agreed to have patient interactions audio recorded , be r and omly assigned to receive/not receive a CD-ROM , have CD-ROM usage monitored ( intervention group ) and complete a follow-up survey . RESULTS Twenty-one of 24 in the intervention group reported using the CD-ROM . Median usage minutes were 63.8 . At follow-up , oncologists rated the CD-ROM from 1 ( " none " or " not at all helpful " ) to 5 ( " a great deal " or " very helpful " ) . Mean responses were : 3.1 and 3.0 for 2 items assessing perceived impact on communications , 3.8 - 4.0 for 6 items assessing perceived helpfulness , 3.0 and 3.10 for 2 items assessing impact on affecting oncologists ' communication with patients and assistance with challenging conversations , respectively , and 3.6 for whether using the CD-ROM was worth their time . Self-report of how much oncologists had used the covered skills before and after intervention showed a perceived increase ( 2.8 before and 3.2 after ) . CONCLUSIONS Findings suggest the tailored interactive CD-ROM has promise for use and acceptance among oncologists . PRACTICE IMPLICATION S If ultimately found effective in changing oncologist 's communication with patients , the CD-ROM 's widespread dissemination should be explored Abstract BACKGROUND : Disclosure of medical errors is encouraged , but research on how patients respond to specific practice s is limited . OBJECTIVE : This study sought to determine whether full disclosure , an existing positive physician-patient relationship , an offer to waive associated costs , and the severity of the clinical outcome influenced patients ’ responses to medical errors . PARTICIPANTS : Four hundred and seven health plan members participated in a r and omized experiment in which they viewed video depictions of medical error and disclosure . DESIGN : Subjects were r and omly assigned to experimental condition . Conditions varied in type of medication error , level of disclosure , reference to a prior positive physician-patient relationship , an offer to waive costs , and clinical outcome . MEASURES : Self-reported likelihood of changing physicians and of seeking legal advice ; satisfaction , trust , and emotional response . RESULTS : Nondisclosure increased the likelihood of changing physicians , and reduced satisfaction and trust in both error conditions . Nondisclosure increased the likelihood of seeking legal advice and was associated with a more negative emotional response in the missed allergy error condition , but did not have a statistically significant impact on seeking legal advice or emotional response in the monitoring error condition . Neither the existence of a positive relationship nor an offer to waive costs had a statistically significant impact . CONCLUSIONS : This study provides evidence that full disclosure is likely to have a positive effect or no effect on how patients respond to medical errors . The clinical outcome also influences patients ’ responses . The impact of an existing positive physician-patient relationship , or of waiving costs associated with the error remains uncertain BACKGROUND Concern regarding financial conflict of interest for physicians has led to calls for disclosure of financial incentives to patients . However , limited data on the outcomes of disclosure exist to guide policy . METHODS This r and omized trial was conducted among 8000 adult patients at 2 multispecialty group practice s based in the Boston , Mass , and Los Angeles , Calif , areas . Intervention patients were mailed a compensation disclosure letter written by the chief medical officer of their physician group , and all patients were surveyed approximately 3 months later . RESULTS Disclosure patients were significantly more able to identify correctly the compensation model of their primary care physician , in Boston ( adjusted odds ratio , 2.30 ; 95 % confidence interval , 1.92 - 2.75 ) and in Los Angeles ( adjusted odds ratio , 1.37 ; 95 % confidence interval , 1.03 - 1.82 ) . Disclosure patients also had more confidence in their ability to judge the possible influence of incentives on their health care : in Boston , 32.5 % vs 17.8 % ( P<.001 ) ; and in Los Angeles , 31.8 % vs 26.4 % ( P = .20 ) . The disclosure intervention did not change trust in primary care physicians overall . However , of patients who remembered receiving the disclosure , 21.4 % in Boston and 24.4 % in Los Angeles responded that the disclosure had increased trust either greatly or somewhat , while in both cities less than 5 % of patients responded that the information decreased trust . Patients ' loyalty to their physician group was higher among disclosure patients in Boston ( 73.4 % vs 70.2 % ; P = .03 ) and Los Angeles ( 74.1 % vs 66.9 % ; P = .08 ) . CONCLUSIONS Among diverse patient population s , a single mailed disclosure letter from physician groups was associated with improved knowledge of physicians ' compensation models . Patients ' trust in their physicians was unharmed , and their loyalty to their physician group was strengthened . For physician groups with similar compensation programs , disclosure to patients should be considered an effective method to enhance the patient-physician relationship BACKGROUND Many physicians receive financial incentives to limit their ordering of expensive tests and procedures . While Medicare m and ates disclosure of incentives , it is not clear how to inform patients without undermining trust . METHODS Our objective was to determine public opinion about physician disclosure of financial incentives and how this might be best communicated to patients . The 2002 General Social Survey included 2765 interviews from a probability sample of English-speaking US households . The interview included questions about financial incentives and an audiotaped scenario of a physician discussing the impact of financial incentives on ordering a magnetic resonance image . Respondents heard 1 of 6 r and omly selected disclosure strategies . The measurements included ratings of trust , satisfaction , agreement with the physician 's decision , and likelihood of remaining with the physician/health plan or seeking a second opinion . RESULTS Nearly half ( 48.8 % ) of respondents had previously heard of financial incentives to limit test ordering . Of the respondents , 94.8 % wanted to be told about incentives , at the time of enrollment in a health plan ( 80.5 % ) , by a health plan representative ( 44.8 % ) , their physician ( 17.1 % ) , or both ( 38.1 % ) . Of the 6 different disclosure strategies , " addressing emotions " and " negotiation " were associated with the best outcomes , while " common enemy " and " denying influences " were most negatively perceived . Black and Hispanic subjects were less likely to express satisfaction or trust and more likely to disenroll or seek a second opinion . CONCLUSIONS The public wants information about physician financial incentives . Specific communication styles enhance how this information is conveyed to patients , increasing trust and supporting the physician-patient relationship OBJECTIVE To assess the impact of patient-centered communication ( PCC ) behaviors on patients ' evaluations of physicians and acceptance of clinical recommendations . METHODS We r and omized 248 patients to view video-recorded , st and ardized vignettes , depicting a cardiologist using a high vs. low degree of PCC while recommending bypass surgery to a patient with angina and 3-vessel coronary artery disease . We compared patients ' ratings of the physician and their decision making in response to the physician 's recommendation , for high vs. low PCC vignettes . RESULTS Patients viewing high PCC vignettes rated the video physician more favorably overall ( 3.01 vs. 2.12 , p<0.001 ) and as more competent ( 3.22 vs. 2.66 , p<0.001 ) and trustworthy ( 2.93 vs. 2.28 , p<0.001 ) than those viewing the low PCC version ( 0 - 4 range for all scales ) . Patients viewing the high PCC version more frequently said they would undergo bypass surgery ( 96 % vs. 74 % , p<0.001 ) if they were the patient in the video . CONCLUSION Patients expressed greater confidence in physicians who used more PCC behaviors , and greater willingness to accept an evidence -based recommendation . PRACTICE IMPLICATION S PCC may make physicians more effective in the delivery of evidence -based care Existing scales to measure trust in physicians have differing content and limited testing . To improve on these measures , a large item pool ( n = 78 ) was generated following a detailed conceptual model and expert review . After pilot testing , the best-performing items were vali date d with a r and om national sample ( n = 9 ) and a regional sample of HMO members ( n = 99 ) . Various psychometric tests produced a 10-item unidimensional scale consistent with most aspects of the conceptual model . Compared with previous scales , the Wake Forest physician trust scale has a somewhat improved combination of internal consistency , variability , and discriminability . The scale is more strongly correlated with satisfaction , desire to remain with a physician , willingness to recommend to friends , and not seeking second opinions ; it is less correlated with insurer trust , membership in managed care , and choice of physician ; and correlations are equivalent with lack of disputes , length of relationship , and number of visits Context Disclosing medical errors is ethically appropriate , but its effect on the doctorpatient relationship and the likelihood of patients seeking legal advice is unknown . Contribution Clinical vignettes and question naires assessing patient opinion were mailed to members of a health maintenance organization . Each vignette varied the type of error , its severity , and the completeness of error disclosure . Respondents indicated that full disclosure improved trust , satisfaction , and emotional response . Decisions to seek legal advice were complex and were not necessarily deflected by full disclosure . Implication s While full disclosure improved patient satisfaction , it did not prevent or increase the likelihood of seeking legal advice . The Editors Since the publication of the Institute of Medicine 's report , To Err Is Human ( 1 ) , the problem of medical errors has gained increased recognition by the general public ( 2 ) . Research ers and policymakers have begun to focus serious efforts on improving patient safety ( 3 - 6 ) , but the complexity and uncertainty inherent in the practice of medicine make it unlikely that medical errors will ever be eliminated completely . When medical errors occur , effective physicianpatient communication is critical . Ethical and professional guidelines emphasize that physicians have a responsibility to disclose medical errors ( 7 - 9 ) , and recent st and ards link disclosure of adverse events to hospital accreditation ( 10 ) . There may also be pragmatic reasons for disclosure patients who pursue litigation may be motivated by a desire for a full explanation of the adverse event ( 11 - 13 ) , and patients may be less likely to sue physicians who provide full and honest explanations ( 14 ) . Although the preponderance of opinion is that disclosure is the right thing to do when a medical error has result ed in patient injury , disclosure often does not occur ( 15 - 20 ) . Several articles ( 21 - 33 ) and continuing medical education material s developed by national organizations ( 34 ) offer guidance , but there is limited empirical literature related to disclosure of medical errors to patients or families ( 11 - 20 , 35 - 41 ) . Of these articles , most focused on whether disclosure occurred or would occur ; few examined the disclosure process or the consequences of disclosure in any way . Thus , the lack of empirical research in this area may be a barrier to disclosure . We therefore undertook a study to assess patients ' views of disclosure . We surveyed a representative sample of members of a large health plan to measure responses to a set of 8 vignettes , each of which described a medical error , the clinical outcome of the error , and a physicianpatient dialogue about the event . The goals of the study were to examine the relationship of the error , severity of clinical outcome , and the level of disclosure to 5 dependent variables : likelihood of changing physicians , likelihood of seeking legal advice , patient satisfaction , trust , and emotional response . We also sought to determine patients ' attitudes , beliefs , and preferences about medical errors and disclosure in general . Methods Sample We conducted a mailed question naire survey of 1500 members of a New Engl and based health maintenance organization . Member names were r and omly sample d from a master list of all health plan members 21 to 85 years of age ( n = 130009 ) . Selected members were sent a letter indicating that they would be receiving the question naire , followed approximately 1 week later by the question naire . A $ 5 cash incentive was enclosed with the question naire . Nonrespondents were sent a reminder postcard 1 week later and a second copy of the question naire 1 week after . The response rate was calculated as the number of usable completed surveys returned ( 958 surveys ) divided by the number of mailed surveys ( 1500 surveys ) minus the number of surveys returned by the mail service as undeliverable ( 47 surveys ) . The study protocol was approved by the institutional review boards of the participating institutions . Question naire Design and Administration The question naire was developed on the basis of a systematic review of the literature ( 11 - 20 , 35 - 41 ) and the results of 2 focus groups comprising 14 patient volunteers . The question naire was refined after pretesting for length and comprehensibility . The final question naire , which is available from the first author , consisted of 4 sections : 1 ) a vignette describing a medication error and the clinical outcome of the error , followed by a physicianpatient dialogue about the error ; 2 ) items assessing participants ' response to the scenario and dialogue ; 3 ) items assessing attitudes , beliefs , and preferences about medical error and disclosure in general ; and 4 ) background and demographic items . Each section is described in detail in this paper . Vignettes and Dialogues Eight versions of the question naire were developed to produce a completely crossed factorial design with 2 levels each of the following variables : type of medication error ( inadequate monitoring of antiepileptic medication vs. prescribing penicillin when penicillin allergy is documented ) , clinical outcome of the error ( life-threatening outcome vs. less serious outcome ) , and level of physician disclosure about the error ( nondisclosure with limited information and responsibility vs. full disclosure with high information , responsibility , and promise to prevent recurrences ) . Figure 1 summarizes the vignette and dialogue combinations comprising each condition , and the Appendix presents them in detail . Each participant received only 1 version ; that is , a single error and outcome vignette with a corresponding dialogue wherein the physician and patient or family member discussed the error and its outcome . Distribution of versions was r and omized . Figure 1 . Description of conditions . Although most medical errors are considered systems errors ( 42 ) rather than the responsibility of individual providers , the actions of the treating physician may contribute to , or mitigate the results of , an error . Furthermore , the physician will often be consideredby the health care team and by the patientto be the most appropriate person to speak to the patient or family after an error has occurred ( 43 - 45 ) . We therefore chose vignettes in which the physician had direct involvement in the error and restricted our focus to the physician as communicator . These decisions were not intended to contradict the importance of a systems approach to patient safety or perpetuate a culture of blame , but rather to provide a starting point for study in this important area . Three items were included to assess whether the vignettes were effective in communicating as intended ; these items queried whether respondents perceived that an error had been made in each scenario and dialogue combination , whether the physician was perceived as responsible , and whether the error was perceived as preventable . Five response options were provided : strongly disagree , disagree , agree , strongly agree , and do n't know . Responses to the Vignette and Dialogue Respondents were instructed to imagine themselves as the patient or family member in the vignette and dialogue and to respond accordingly . Two items , developed for this study , focused on behavior . Respondents were asked to indicate whether they would change physicians or seek legal advice . The same 5 response options mentioned earlier were provided . For the analysis , responses were recoded to be dichotomous , with agree or strongly agree responses compared with all others . Patient satisfaction was assessed by using 5 items drawn from the American Board of Internal Medicine Patient Satisfaction Question naire ( 46 ) . Trust in the physician was assessed by using 8 items drawn from the Trust in Physician Scale ( 47 ) plus 1 supplemental item ( This doctor seemed to be withholding important information . ) . Item wording was modified slightly to refer to the vignette rather than a real encounter . Five semantic differential items were developed for this study to assess emotional response : angry or calm , frightened or reassured , worried or relieved , wronged or respected , and dissatisfied or satisfied . All were on a 5-point scale ; the most positive response option ( for example , reassured ) was assigned a value of 5 , and the most negative response option ( for example , worried ) was assigned a value of 1 . The variable emotional response was computed as the mean across the 5 semantic differential items , with higher scores indicating a more positive emotional response . Attitudes , Beliefs , and Preferences about Medical Error and Disclosure A set of 9 items was developed on the basis of the focus group interviews and a review of the literature to measure attitudes and beliefs about medical errors and disclosure in general . Five response options were provided : strongly disagree , disagree , neutral , agree , and strongly agree . Nine items were developed to assess respondents ' preferences for action after a medical error . These items were also based on the review of the literature on disclosure and were intended to directly assess preferences for commonly recommended responses to error ( for example , I would want to know the full details of how the error occurred . ) . Again , 5 response options were provided : strongly disagree , disagree , neutral , agree , and strongly agree . Background and Demographic Items Final items queried personal experience with medical error or injury , history of having filed a lawsuit against a physician or other health care provider , sex , education , age , and race or ethnicity . Statistical Analysis We compared background characteristics of respondents and nonrespondents by using a chi-square test for sex and a t-test for age . Associations between the 3 design variables ( type of medication error , severity of clinical outcome , and level of disclosure ) and the 2 dichotomously coded variables ( likelihood of changing physicians and likelihood of seeking legal advice ) were modeled by using logistic regression OBJECTIVE To determine how patients in different kinds of practice s -- solo or single specialty ( SOLO ) , multispecialty group ( MSG ) , or health maintenance organizations (HMOs)-- and with fee-for-service ( FFS ) or prepaid physician payment arrangements evaluate their medical care . DESIGN Survey of adult out patients after office visits , with sample weighted to represent population of patients visiting physicians in each practice type . SETTING Offices of 367 internists , family practitioners , endocrinologists , cardiologists , and nurse practitioners , in HMOs ( prepaid only ) , MSGs ( prepaid and FFS ) , and SOLO practice s ( prepaid and FFS ) . PATIENTS Adults ( N = 17,671 ) at start of the Medical Outcomes Study . OUTCOME MEASURES Overall rating of the visit ( five choices from excellent to poor ) . A r and om half of the sample also rated the provider 's technical skills , personal manner , and explanations of care as well as time spent during the visit , the appointment wait , the office wait , the convenience of the office location , and telephone access . RESULTS Fifty-five percent of patients rated their visit overall as excellent , 32 % very good , 11 % good , and 2 % fair or poor . Patients of SOLO practitioners were more likely ( 64 % ) to rate their visit excellent than MSG ( 48 % ) or HMO ( 49 % ) patients ( P < .001 ) . Patients of SOLO practitioners rated all aspects of care better than HMO patients did , most markedly appointment waits ( 64 % vs 40 % excellent ; P < .0001 ) and telephone access ( 64 % vs 33 % excellent ; P < .0001 ) . Within SOLO and MSG practice s , FFS patients rated most specific aspects better than prepaid patients , but these differences were not statistically significant and were inconsistent across cities . Adjusting for patients ' demographics , diagnoses and self-rated health did not change results . Physicians with visit ratings in the lowest 20 % were nearly four times as likely to be left by patients within 6 months than physicians in the highest 20 % ( 16.7 % vs 4.6 % ; P < .001 ) . CONCLUSION Of the five practice type and payment method combinations , SOLO FFS patients rated their visits best and HMO patients worst . Whether FFS or prepaid , care was rated better in small than in large practice s. Our study shows that a brief visit rating form can be used to compare practice setting s and health plans , and that patient ratings predict what proportion of patients , on average , will leave their physicians in the next several months Background . Conceptual or theoretical analysts of trust in medical setting s distinguish among markedly different objects or types of trust . However , little is known about how similar or different these types of trust are in reality and the relationship of trust with satisfaction . Objectives . This exploratory study conducted a comparison among trust in one ’s personal physician , health insurer , and in the medical profession , and examined whether the relationship between trust and satisfaction differs according to the type of trust in question . Research Design . R and om national telephone survey using vali date d multi-item measures of trust and satisfaction . Subjects . A total of 1117 individuals aged 20 years and older with health insurance and reporting 2 healthcare professional visits in the past 2 years . Results . Rank-order correlation analyses find that both physician and insurer trust are sensitive to the amount of contact the patient has had and their adequacy of choice in selecting the physician or insurer . Trust in the medical profession st and s out as being uniquely related to patients ’ desire to seek care and their preference for how much control physicians should have in making medical decisions . Adding satisfaction to the models reduced the number of significant predictors of insurance trust disproportionately . Conclusions . Consistent with theory , we found both substantial similarities and notable differences in the sets of factors that predict 3 different types of trust . Trust and satisfaction are much less distinct with respect to health insurers than with respect to physicians or the medical profession OBJECTIVE To develop a scale to measure patients ' trust in health insurers , including public and private insurers and both indemnity and managed care . A scale was developed based on our conceptual model of insurer trust . The scale was analyzed for its factor structure , internal consistency , construct validity , and other psychometric properties . DATA SOURCES / STUDY SETTING The scale was developed and vali date d on a r and om national sample ( n = 410 ) of subjects with any type of insurance and further vali date d and used in a regional r and om sample of members of an HMO in North Carolina ( n = 1152 ) . STUDY DESIGN Factor analysis was used to uncover the underlying dimensions of the scale . Internal consistency was assessed by Cronbach 's alpha . Construct validity was established by Pearson or Spearman correlations and t tests . DATA COLLECTION Data were collected via telephone interviews . PRINCIPAL FINDINGS The 11-item scale has good internal consistency ( alpha = 0.92/ 0.89 ) and response variability ( range = 11 - 55 , M = 36.5/37.0 , SD = 7.8/7.0 ) . Insurer trust is a unidimensional construct and is related to trust in physicians , satisfaction with care and with insurer , having enough choice in selecting health insurer , no prior disputes with health insurer , type of insurer , and desire to remain with insurer . CONCLUSIONS Trust in health insurers can be validly and reliably measured . Additional studies are required to learn more about what factors affect insurer trust and whether differences and changes in insurer trust affect actual behaviors and other outcomes of interest Abstract OBJECTIVE : To evaluate the impact of an intervention design ed to help patients choose a new primary care provider ( PCP ) compared with the usual method of assigning patients to a new PCP . DESIGN : R and omized controlled trial conducted between November 1998 and June 2000 . INTERVENTION : Provision of telephone or web-based provider-specific information to aid in the selection of a provider . SETTING : Medical center within a large HMO . PATIENTS : One thous and and ninety patients who were ≥30 years old , whose previous PCP had retired and who responded to a mailed question naire 1 year after linkage with a new PCP . MEASUREMENTS AND MAIN RESULTS : The question naire assessed perceptions of choice , satisfaction , trust , and retention of the PCP . During the intervention period , 85 % of subjects obtained a new PCP . Intervention subjects were more likely to perceive that they chose their PCP ( 78 % vs 22 % ; P<.001 ) , to retain their PCP at 1 year ( 93 % vs 69 % ; P<.001 ) , and to report greater overall satisfaction with the PCP ( 67 % vs 57 % ; P<.01 ) , compared to control subjects who were assigned to a PCP . The intervention subjects also reported greater trust in their PCP on most measures , but these differences did not remain statistically significant after adjustments for patient age , gender , ethnicity , education , and health status . CONCLUSIONS : Encouraging patients to choose their PCP can result in mutually beneficial outcomes for both patients and providers , such as greater overall satisfaction and duration of the relationship . Further research is needed to identify the types of information most useful in making this choice and to underst and the relevant underlying patient expectations Managed care needs effective and efficient ways to orient new members , enhance trust and loyalty , and offer prevention and self-care education and services . Recent adult enrollees of Kaiser Permanente ( Northern California ) were r and omly assigned to one of three intervention conditions ( n = 286 ) ( individual visit with a physician , physician visit plus a visit with a health educator , a group visit of eight new members led by a physician and health educator ) or a r and om control group ( n = 278 ) . Outcomes were gauged via pre- and post-visit question naires and a 20-min telephone survey at baseline and at a 6-month follow-up . Compared to controls , attendees of the three interventions had higher satisfaction , self-rated prevention knowledge , acceptance of health plan guidelines , and were more likely to plan to remain in the health plan . Group visit attendees stood out as experiencing the greatest benefits and were especially likely to report saving a telephone call or visit to their doctor by using a self-care h and book OBJECTIVE To determine whether an intervention design ed to inform and guide patients in choosing a primary care provider ( PCP ) could increase satisfaction and trust . DESIGN A r and omized controlled trial conducted at the Santa Clara Medical Center of the Kaiser Permanente Medical Care Program in Northern California . PATIENTS AND METHODS Patients needing a PCP were r and omly assigned to Informed Choice ( provider-level information offered ) , Guided Choice ( PCP names provided based on the similarity of patients ' and practitioners ' patient-centered beliefs , and patients then chose ) , or Usual Care . One year later , mailed question naires asked about patients ' trust and satisfaction , perceptions of the choice process , and trust and satisfaction with Kaiser Permanente . More than 5000 adult patients were linked with a PCP as part of the project , and completed surveys were returned by 2437 patients . RESULTS Neither intervention arm generated better matches on patient-practitioner beliefs than Usual Care ; however , trust and satisfaction were higher among Guided Choice patients . Across study arms , patient-practitioner belief discrepancy showed a consistent positive association with trust , satisfaction , and attitudes toward Kaiser Permanente . CONCLUSIONS The discrepancy between patient and practitioner beliefs about care is an important determinant of trust and satisfaction , and involving patients in the selection of their PCP can have an independent positive effect . It should be possible to build on the experience of this project to develop programs that better match patients and practitioners within managed care plans Scores on the Rotter Interpersonal Trust Scale were evaluated as predictors of psychological well-being , functional health , and longevity in a sample of 100 men and women who were between 55 and 80 years old at baseline ( mean age 66.8 ) . Cross-sectionally , high levels of trust were associated with better self-rated health and more life satisfaction . Follow-up over approximately 8 years found baseline levels of trust to be positively related to subsequent functional health , but not to subsequent life satisfaction . Mortality follow-up after 14 years demonstrated that those with high levels of trust had longer survival ( p = .03 ) , a finding that was somewhat weakened by controlling for baseline health ratings . These findings illustrate the health protective effects of high levels of trust and suggest the potential usefulness of the trust concept for underst and ing successful aging BACKGROUND Despite high prevalence , emotional distress among primary care patients often goes unrecognized during routine medical encounters . OBJECTIVE To explore the effect of communication-skills training on the process and outcome of care associated with patients ' emotional distress . METHODS A r and omized , controlled field trial was conducted with 69 primary care physicians and 648 of their patients . Physicians were r and omized to a no-training control group or one of two communication-skills training courses design ed to help physicians address patients ' emotional distress . The two training courses addressed communication through problem-defining skills or emotion-h and ling skills . All office visits of study physicians were audiotaped until five emotionally distressed and five nondistressed patients were enrolled based on patient response to the General Health Question naire . Physicians were also audiotaped interviewing a simulated patient to evaluate clinical proficiency . Telephone monitoring of distressed patients for utilization of medical services and General Health Question naire scores was conducted 2 weeks , 3 months , and 6 months after their audiotaped office visits . RESULTS Audiotape analysis of actual and simulated patients showed that trained physicians used significantly more problem-defining and emotion-h and ling skills than did untrained physicians , without increasing the length of the visit . Trained physicians also reported more psychosocial problems , engaged in more strategies for managing emotional problems with actual patients , and scored higher in clinical proficiency with simulated patients . Patients of trained physicians reported reduction in emotional distress for as long as 6 months . CONCLUSIONS Important changes in physicians ' communication skills were evident after an 8-hour program . The training improved the process and outcome of care without lengthening the visits Opinions are deeply divided over whether rewarding physicians for lowering costs decreases trust in physicians or insurers . To explore the effects of disclosing physician payment methods in HMOs , members of two similar HMO plans were r and omized to intervention and control groups , and the experimental arm was told how the HMO paid their primary care physician . Separate disclosures were developed for each plan , one describing primarily capitation payment , and the other ( mixed-incentive plan ) describing fee-for-service payment with a bonus that rewards cost savings , satisfaction , and preventive services . The disclosures pointed out more of the positive than the negative features of these incentives . We found that the disclosures doubled the number of subjects with substantial knowledge of the physician incentives and halved the number with no knowledge . Nevertheless , the disclosures had no negative effects on trust of either physicians or insurers . The capitated plan disclosure had a small positive effect on trust of physicians . Disclosing the positive and negative features of incentives and increasing knowledge of these incentives does not , in the short term , reduce trust in physicians or insurers and may have a mild positive impact on physician trust , perhaps as a consequence of displaying c and or and increasing underst and ing of positive features OBJECTIVE Most studies of trust in the medical arena have focused on trust in physicians rather than trust in health insurers , and have been cross-sectional rather than longitudinal studies . This study examined associations among trust in a managed care insurer , trust in one 's primary physician , and subsequent enrollee behaviors relating to source of care . The study also documents changes in trust in the study population following the disclosure of physician incentives . STUDY SETTING A medium-sized ( 300,000 member ) HMO , located in the southeastern United States . DATA COLLECTION One to two years after baseline , we r and omly resurveyed a quarter ( n = 558 ) of the initial study population of a large intervention study design ed to measure the impact of disclosing HMO financial incentives on patient trust . This follow-up study was also design ed to measure the effects of trust on source of care . ANALYSES Multivariate regression analyses of survey data examined associations between baseline levels of trust and subsequent enrollee behaviors such as using a non-PCP physician without a PCP referral , as well as changes in trust since baseline . RESULTS High baseline insurer trust was associated with a lower probability of a patient seeking care from a non-PCP physician ( OR = 0.55 , 95 percent CI : 0.33 , 0.91 ) . No long-term effects of prior disclosure of financial incentives were observed . Overall , there was a slight increase in overall trust in the insurer ( 1.8 percent , p < .05 ) but no change in trust in one 's primary physician . The increase in insurer trust was primarily restricted to 23 percent of the enrollees who had changed their PCPs following the baseline survey ( 6.6 percent , p < .01 ) . In multivariate analyses , changing physicians was the most significant predictor of increased insurer trust ( OR = 2.17 , 95 percent CI : 1.37 , 3.43 ) . CONCLUSIONS . Trust in one 's insurer seems to change over time more than trust in one 's primary physician , and is predictive of enrollee behaviors such as seeking care from other physicians . The ability to change physicians seems to increase trust in the insurer BACKGROUND : Internet-based interventions for education and behavior change have proliferated , but most adolescents may not be sufficiently motivated to engage in Internet-based behavior change interventions . We sought to determine how two different forms of primary care physician engagement , brief advice ( BA ) versus motivational interview ( MI ) , could enhance participation outcomes in an Internet-based depression prevention intervention . METHODS : Eighty-three adolescents at risk for developing major depression were recruited by screening in primary care and r and omized to two groups : BA ( 1 - 2 minutes ) + Internet program versus MI ( 10 - 15 minutes ) + Internet program . We compared measures of participation and satisfaction for the two groups for a minimum of 12 months after enrollment . RESULTS : Both groups engaged the site actively ( MI : 90 % versus BA : 78 % , p=0.12 ) . MI had significantly higher levels of engagement than BA for measures including total time on site ( 143.7 minutes versus 100.2 minutes , p=0.03 ) , number of sessions ( 8.16 versus 6.00 , p=0.04 ) , longer duration of session activity on Internet site ( 46.2 days versus 29.34 days , p=0.04 ) , and with more characters typed into exercises ( 3532 versus 2004 , p=0.01 ) . Adolescents in the MI group reported higher trust in their physician ( 4.18 versus 3.74 , p=0.05 ) and greater satisfaction with the Internet-based component ( 7.92 versus 6.66 , p=0.01 ) . CONCLUSIONS : Primary care engagement , particularly using motivational interviewing , may increase Internet use dose , and some elements enhance and intensify adolescent use of an Internet-based intervention over a one to two month period . Primary care engagement may be a useful method to facilitate adolescent involvement in preventive mental health interventions ABSTRACT BACKGROUND There is consensus that patients should be told if they are injured by medical care . However , there is little information on how they react to different methods of disclosure . OBJECTIVE To determine if volunteers ’ reactions to videos of physicians disclosing adverse events are related to the physician apologizing and accepting responsibility . DESIGN Survey of viewers r and omized to watch videos of disclosures of three adverse events ( missed mammogram , chemotherapy overdose , delay in surgical therapy ) with design ed variations in extent of apology ( full , non-specific , none ) and acceptance of responsibility ( full , none ) . PARTICIPANTS Adult volunteer sample from the general community in Baltimore . MEASUREMENTS Viewer evaluations of physicians in the videos using st and ardized scales . RESULTS Of 200 volunteers , 50 % were < 40 years , 25 % were female , 80 % were African American , and 50 % had completed high school . For design ed variations , scores were non-significantly higher for full apology/responsibility , and lower for no apology/no responsibility . Perceived apology or responsibility was related to significantly higher ratings ( chi-square , 81 % vs. 38 % trusted ; 56 % vs. 27 % would refer , p < 0.05 ) , but inclination to sue was unchanged ( 43 % vs. 47 % ) . In logistic regression analyses adjusting for age , gender , race and education , perceived apology and perceived responsibility were independently related to higher ratings for all measures . Inclination to sue was reduced non-significantly . CONCLUSIONS Patients will probably respond more favorably to physicians who apologize and accept responsibility for medical errors than those who do not apologize or give ambiguous responses . Patient perceptions of what is said may be more important than what is actually said . Desire to sue may not be affected despite a full apology and acceptance of responsibility Patient trust in the physician is an important aspect of the patient-physician relationship that has recently become a focus of interest , in part due to the rise of managed care in the US healthcare system . In a previous study , we identified physician behaviours reported by patients as important to establishing their trust in the physician . The current study attempted to modify these behaviours via a short training programme and thereby to increase patient trust and improve associated outcomes . After baseline measurements , 10 physicians were r and omized to the intervention group and 10 remained as a control group . While intervention physicians showed a net improvement in 16 of 19 specific patient-reported behaviours when compared to control physicians , these differences were not statistically significant . There was also no significant difference in patient trust , patient satisfaction , continuity , self-reported adherence , number of referrals or number of diagnostic tests ordered . This short training course in a group of self-selected physicians was not a sufficiently strong intervention to achieve the desired effect . Suggestions are given for design ing a stronger training intervention OBJECTIVES To further vali date and assess the reliability and validity of the Trust in Physician Scale . METHODS Consecutive adult patients ( n = 414 ) from 20 community-based , primary care practice s were enrolled in a prospect i ve , 6-month study . At enrollment , subjects completed the 11-item Trust in Physician Scale plus measures of demographics , preferences for care , and satisfaction with care received from the physician . Continuity , satisfaction with care , and self-reported adherence to treatment were measured at 6 months . Reliability , construct validity , and predictive validity were assessed using correlation coefficients and analysis of variance techniques . RESULTS The Trust in Physician Scale showed high internal consistency ( Cronbach 's alpha = .89 ) and good 1-month test-retest reliability ( intraclass correlation coefficient = .77 ) . As expected , trust increased with the length of the relationship and was higher among patients who actively chose their physician , who preferred more physician involvement , and who expected their physician to care for a larger proportion of their problems ( P < 0.001 for all associations ) . Baseline trust predicted continuity with the physician , self-reported adherence to medication , and satisfaction at 6 months after adjustment for gender , age , education , length of the relationship , active choice of the physician , and preferences for care . After additional adjustment for baseline satisfaction with physician care , trust remained a significant predictor of continuity , adherence , and satisfaction . CONCLUSIONS The Trust in Physician Scale has desirable psychometric characteristics and demonstrates construct and predictive validity . It appears to be related to , but still distinct from , patient satisfaction with the physician and , thus , provides a valuable additional measure for assessment of the quality of the patient-physician relationship BACKGROUND Quality cancer care requires addressing patients ' emotions , which oncologists infrequently do . Multiday courses can teach oncologists skills to h and le emotion ; however , such workshops are long and costly . OBJECTIVE To test whether a brief , computerized intervention improves oncologist responses to patient expressions of negative emotion . DESIGN R and omized , controlled , parallel-group trial stratified by site , sex , and oncologic specialty . Oncologists were r and omly assigned to receive a communication lecture or the lecture plus a tailored CD-ROM . ( Clinical Trials.gov registration number : NCT00276627 ) SETTING Oncology clinics at a comprehensive cancer center and Veterans Affairs Medical Center in Durham , North Carolina , and a comprehensive cancer center in Pittsburgh , Pennsylvania . PARTICIPANTS 48 medical , gynecologic , and radiation oncologists and 264 patients with advanced cancer . INTERVENTION Oncologists were r and omly assigned in a 1:1 ratio to receive an interactive CD-ROM about responding to patients ' negative emotions . The CD-ROM included tailored feedback on the oncologists ' own recorded conversations . MEASUREMENTS Postintervention audio recordings were used to identify the number of empathic statements and responses to patients ' expressions of negative emotion . Surveys evaluated patients ' trust in their oncologists and perceptions of their oncologists ' communication skills . RESULTS Oncologists in the intervention group used more empathic statements ( relative risk , 1.9 [ 95 % CI , 1.1 to 3.3 ] ; P = 0.024 ) and were more likely to respond to negative emotions empathically ( odds ratio , 2.1 [ CI , 1.1 to 4.2 ] ; P = 0.028 ) than control oncologists . Patients of intervention oncologists reported greater trust in their oncologists than did patients of control oncologists ( estimated mean difference , 0.1 [ CI , 0.0 to 0.2 ] ; P = 0.036 ) . There was no significant difference in perceptions of communication skills . LIMITATIONS Long-term effects were not examined . The findings may not be generalizable outside of academic medical centers . CONCLUSION A brief computerized intervention improves how oncologists respond to patients ' expressions of negative emotions . PRIMARY FUNDING SOURCE National Cancer Institute |
469 | 22,895,983 | There is no evidence available from r and omized controlled trials on which to base a judgment about the effectiveness of music education for the improvement of reading skills in children and adolescents with dyslexia . | BACKGROUND Dyslexia ( or developmental dyslexia or specific reading disability ) is a specific learning disorder that has a neurobiological origin .
It is marked by difficulties with accurate or fluent recognition of words and poor spelling in people who have average or above average intelligence and these difficulties can not be attributed to another cause , for example , poor vision , hearing difficulty , or lack of socio-environmental opportunities , motivation , or adequate instruction .
Studies have correlated reading skills with musical abilities .
It has been hypothesized that musical training may be able to remediate timing difficulties , improve pitch perception , or increase spatial awareness , thereby having a positive effect on skills needed in the development of language and literacy .
OBJECTIVES To study the effectiveness of music education on reading skills ( that is , oral reading skills , reading comprehension , reading fluency , phonological awareness , and spelling ) in children and adolescents with dyslexia . | The main aim of the present experiment was to determine whether extensive musical training facilitates pitch contour processing not only in music but also in language . We used a parametric manipulation of final notes ' or words ' fundamental frequency ( F0 ) , and we recorded behavioral and electrophysiological data to examine the precise time course of pitch processing . We compared professional musicians and nonmusicians . Results revealed that within both domains , musicians detected weak F0 manipulations better than nonmusicians . Moreover , F0 manipulations within both music and language elicited similar variations in brain electrical potentials , with overall shorter onset latency for musicians than for nonmusicians . Finally , the scalp distribution of an early negativity in the linguistic task varied with musical expertise , being largest over temporal sites bilaterally for musicians and largest central ly and over left temporal sites for nonmusicians . These results are taken as evidence that extensive musical training influences the perception of pitch contour in spoken language The idea that music makes you smarter has received considerable attention from scholars and the media . The present report is the first to test this hypothesis directly with r and om assignment of a large sample of children ( N = 144 ) to two different types of music lessons ( keyboard or voice ) or to control groups that received drama lessons or no lessons . IQ was measured before and after the lessons . Compared with children in the control groups , children in the music groups exhibited greater increases in full-scale IQ . The effect was relatively small , but it generalized across IQ subtests , index scores , and a st and ardized measure of academic achievement . Unexpectedly , children in the drama group exhibited substantial pre- to post-test improvements in adaptive social behavior that were not evident in the music groups We conducted a longitudinal study with 32 nonmusician children over 9 months to determine 1 ) whether functional differences between musician and nonmusician children reflect specific predispositions for music or result from musical training and 2 ) whether musical training improves nonmusical brain functions such as reading and linguistic pitch processing . Event-related brain potentials were recorded while 8-year-old children performed tasks design ed to test the hypothesis that musical training improves pitch processing not only in music but also in speech . Following the first testing sessions nonmusician children were pseudor and omly assigned to music or to painting training for 6 months and were tested again after training using the same tests . After musical ( but not painting ) training , children showed enhanced reading and pitch discrimination abilities in speech . Remarkably , 6 months of musical training thus suffices to significantly improve behavior and to influence the development of neural processes as reflected in specific pattern of brain waves . These results reveal positive transfer from music to speech and highlight the influence of musical training . Finally , they demonstrate brain plasticity in showing that relatively short periods of training have strong consequences on the functional organization of the children 's brain The purpose of the present study was to determine the efficacy of using music as a remedial strategy to enhance the reading skills of second- grade students and students who have been identified as having a specific learning disability ( SLD ) in reading . First , an intensive short-term music curriculum was design ed to target reading comprehension and vocabulary skills at the second grade level . The curriculum was then implemented in classrooms at two public schools in the Southeast . Reading skills were evaluated pre and post curriculum intervention via the vocabulary and reading comprehension subtests of the Gates-MacGinitie Reading Test for second grade . Analysis of pre/posttest data revealed that students with a specific disability in reading improved significantly from pre to post on all three subtests : word decoding ( p = .04 ) , word knowledge ( p = .01 ) , reading comprehension ( p = .01 ) , and test total ( p = .01 ) . Paired t-tests revealed that for 2nd grade students , both treatment and control classes improved significantly from pre to post on the subtests word decoding , word knowledge , and test total . While both classes made gains from pre to post on the subtest , reading comprehension , neither improved significantly . Analysis of Covariance revealed that the treatment class made greater gains pre to post than the control class on all 3 subtests ( Including reading comprehension ) , and significantly greater gains on the subtest , word knowledge ( p = .01 ) |
470 | 23,041,096 | Hypertension remains a common complication following aortic coa rct ation repair . | UNLABELLED Hypertension continues to be a common and potentially serious problem in patients who have undergone anatomically successful repair of aortic coa rct ation .
OBJECTIVE To assess the prevalence of hypertension after aortic coa rct ation repair , the factors that affect the prevalence and the hypotheses behind hypertension in this cohort of patients . | Background — Patients with repaired coa rct ation are at increased risk of hypertension and cardiovascular disease despite successful repair . We studied the function of conduit arteries in upper and lower limbs of patients late after successful coa rct ation repair and its relation to age at surgery . Methods and Results —Flow-mediated dilatation ( FMD ) and the dilatation after sublingual nitroglycerin ( NTG , 25 & mgr;g ) were measured by using high-resolution ultrasound in the brachial artery in 64 coa rct ation patients ( 44 males and 20 females , aged 19±10 years ; median age at operation 4 months ) and 45 control subjects ( 28 males and 17 females , aged 19±10 years ) and in the posterior tibial artery in 37 patients and 22 control subjects . Arterial stiffness was determined by pulse-wave velocity ( PWV ) of the brachioradial and femoral-dorsalis pedis tracts . Patients , compared with control subjects , had lower brachial FMD ( 7.16±3.4 % versus 8.62±2.3 % , respectively;P = 0.02 ) and NTG ( 11.46±4.3 % versus 13.21±4.6 % , respectively;P = 0.046 ) and higher brachioradial PWV ( 9.17±3.1 versus 8.06±1.9 m/s , respectively;P = 0.05 ) . In contrast , posterior tibial FMD , NTG , and lower limb PWV were comparable . Age ( months ) at the time of repair was related to brachioradial PWV ( r = 0.42 , P = 0.002 ) but not to brachial FMD or NTG . Conclusions — Patients with repaired aortic coa rct ation have impaired conduit artery function , with abnormal responses to flow and NTG , and increased vascular stiffness confined to the upper part of the body . Early repair is associated with preserved elastic properties of conduit arteries , but reduced reactivity remains Introduction : Since the 1980s , stent implantation has evolved as an important therapeutic strategy for coa rct ation of the aorta . However , available data is frequently flawed by short follow‐up , lack of adequate follow‐up imaging , and retrospective nature of data collection . Methods : Data was prospect ively collected using a multicenter registry congenital cardiovascular interventional study consortium ( CCISC ) . Between 2000 and 2009 , 302 patients from 34 centers with a median weight of 58 kg underwent stent implantation for coa rct ation . Eligible patients ( 44 % ) completed intermediate follow‐up ( 3–18 months ) with integrated imaging ( cath , CT , MRI ) , whereas 21 % completed long‐term follow‐up ( > 18–60 months ) . Procedural success was defined as UL/LL systolic gradient of less than 20 mm Hg , lack of significant recurrent obstruction , and freedom from unplanned repeat intervention . Results : Acute procedural success was 96 % . Cumulative intermediate success was 86 % , and cumulative long‐term success was 77 % . Unplanned repeat interventions were required in 4 % , and aortic wall complications were seen in 1 % of patients ( dissection n = 1 and aneurysm n = 3 ) . Other adverse events ( n = 15 ) occurred mainly acutely and included technical complications such as stent malposition ( n = 9 ) . At long‐term follow‐up , 23 % of patients continued to have systolic blood pressure above the 95th centile , 9 % had an upper‐to‐lower limb blood pressure gradient in excess of 20 mm Hg , and 32 % were taking antihypertensive medication . Conclusions : This study documented acute , intermediate , and long‐term outcome data comparable or superior with other surgical or interventional series . However , even with successful initial stent therapy , patients continue to require long‐term follow‐up and have associated long‐term morbidity , relating to aortic wall complications , systemic hypertension , recurrent obstruction as well as need for repeat intervention . © 2010 Wiley‐Liss , Although reference values for ambulatory blood pressure ( ABP ) monitoring have been investigated in several population studies , these values were derived from cross-sectional observations and were based merely on the statistical distribution of blood pressure values . Therefore , we conducted a prospect i ve cohort study to identify reference values for 24-hour ABP in relation to prognosis . We obtained measurements of 24-hour ABP for 1542 subjects ( 565 men ) aged 40 years and over in a general population of a rural Japanese community and then followed-up their survival status . There were 117 deaths during the follow-up period ( mean , 6.2 years ) . The association between baseline 24-hour ABP values and mortality , examined by the Cox proportional hazards regression model adjusted for possible confounding factors , showed a better fit with a second-degree equation than with a first-degree equation . On the basis of the results of this analysis , we identified the following reference values as the optimal blood pressure ranges that predict the best prognosis : 120 to 133 mm Hg for systolic blood pressure and 65 to 78 mm Hg for diastolic blood pressure . 24-Hour ABP values > 134/79 mm Hg and < 119/64 mm Hg were related to increased risks for cardiovascular and noncardiovascular mortality , respectively . This is the first report to propose reference values for 24-hour ABP based on a prognostic criterion OBJECTIVES The purpose of this study was to evaluate the effect of ramipril on endothelial function and inflammatory process in a group of normotensive subjects with successfully repaired coa rct ation of the aorta ( SCR ) . BACKGROUND Subjects with SCR experience higher long-term cardiovascular risk as a result of the relapse of arterial hypertension or owing to nonreversible structural changes in the pre-coa rct ation arterial tree . These subjects experience endothelial dysfunction in the right forearm and appear to have elevated levels of proatherogenic inflammatory markers , even in the absence of arterial hypertension . METHODS Twenty young individuals age 27.3 + /- 2.4 years old with SCR 13.9 + /- 2.2 years previously , received ramipril 5 mg/day for 4 weeks in a r and omized , cross-over , controlled trial . Endothelial function was evaluated in the right forearm by gauge-strain plethysmography , and serum levels of interleukin (IL)-1b , IL-6 , soluble CD40 lig and ( sCD40L ) , and soluble vascular cell adhesion molecule (sVCAM)-1 were determined by enzyme-linked immunosorbent assay . RESULTS Ramipril improved endothelial function ( p < 0.001 ) and decreased the expression of proinflammatory cytokine IL-6 ( p < 0.05 ) and sCD40L ( p < 0.01 ) . Furthermore , ramipril decreased serum levels of sVCAM-1 ( p < 0.01 ) but failed to affect serum levels of C-reactive protein . These effects were independent of blood pressure lowering . CONCLUSIONS Ramipril reversed the impaired endothelial function and decreased the expression of proinflammatory cytokine IL-6 , sCD40L , and adhesion molecules in normotensive subjects with SCR . These findings imply that ramipril treatment may have antiatherogenic effects in subjects with SCR , even in the absence of arterial hypertension OBJECTIVES This study was design ed to investigate the influence of aortic arch geometry on vascular remodeling after anatomically successful repair of coa rct ation of the aorta ( CoA ) . BACKGROUND Abnormalities of the precoa rct ation vasculature are known to occur after CoA repair and appear related to adverse outcomes . The influence of aortic arch geometry on such abnormalities is unknown . METHODS Sixty-three postcoa rct ectomy subjects ( age 15.9 + /- 6.3 years ) were compared with 63 control volunteers . Aortic arch shape was characterized on magnetic resonance imaging using both qualitative classification , identifying 3 subtypes of arch geometry ( Gothic , Crenel , Romanesque ) , and a quantitative index , height/width ratio ( H/W ) of the aorta . Using ultrasound , we measured carotid artery intima-media thickness ( IMT ) and stiffness index and distensibility , as well as right brachial artery flow-mediated dilation ( FMD ) and glyceryl trinitate (GTN)-induced dilatation , to assess the precoa rct ation vasculature of these subjects . RESULTS Gothic arch type was associated with higher carotid IMT and stiffness index , lower carotid distensibility ( p < 0.001 for all ) , and lower brachial reactivity ( FMD , p < 0.01 ; GTN response , p < 0.001 ) compared with Crenel and Romanesque geometries and with control subjects . The height/width ratio was also significantly related to these vascular abnormalities . Even in CoA subjects with Romanesque arch geometry , arterial function and stiffness parameters were significantly impaired compared with control subjects . CONCLUSIONS In young adult survivors of anatomically successful CoA repair , a gothic-type aortic arch with high H/W is associated with abnormal IMT , higher aortic stiffness index , and impaired arterial reactivity in the pre-CoA vasculature Chronic hypertension is a major concern in adults who have undergone resection of coa rct ation of the aorta ( CoA ) in childhood . In otherwise healthy subjects , exercise-induced hypertension is prognostic for chronic hypertension ; however , the prognostic value in patients with CoA remains unknown . The aim of the present study was to evaluate the predictive value of exercise-induced hypertension for chronic hypertension in these patients . In the present prospect i ve follow-up study , 74 patients with CoA ( 58 % men , age 30.9 ± 9.5 years ) underwent ambulatory blood pressure ( BP ) monitoring and exercise testing twice from 2001 to 2009 with a follow-up period of 6.3 ± 0.8 years . Hypertension was defined as a mean systolic BP ≥140 mm Hg and /or mean diastolic BP ≥90 mm Hg or the need for antihypertensive treatment . Exercise-induced hypertension was defined as a mean systolic BP of < 140 mm Hg and peak exercise systolic BP of ≥200 mm Hg . At baseline , 27 patients ( 36 % ) were hypertensive , 11 ( 15 % ) had exercise-induced hypertension , and 36 ( 49 % ) were normotensive . At follow-up , all 27 hypertensive patients remained hypertensive . Of the 11 with exercise-induced hypertension , 7 ( 64 % ) had developed chronic hypertension , and 4 ( 36 % ) continued to have exercise-induced hypertension . Of the 36 normotensive patients , 7 ( 19 % ) had developed hypertension , 12 ( 33 % ) had developed exercise-induced hypertension , and 17 ( 47 % ) remained normotensive . On multivariate analysis , baseline maximum exercise systolic BP was independently associated with the mean systolic BP at follow-up ( β = 0.13 , p = 0.005 ) . In conclusion , the maximum exercise systolic BP was a predictor for chronic hypertension in patients with CoA. These findings demonstrate the clinical importance of exercise-induced hypertension and warrant additional study into the long-term consequences of exercise-induced hypertension and the potential beneficial role of early antihypertensive treatment in adult patients after CoA repair with exercise-induced hypertension Even after successful repair , hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coa rct ation ( CoA ) . We compared the effect of c and esartan ( angiotensin II receptor blockade ) and metoprolol ( beta-adrenergic receptor blockade ) on blood pressure , large artery stiffness , and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label , crossover study , hypertensive patients after CoA repair were first r and omly assigned to treatment with c and esartan 8 mg or metoprolol 100 mg once per day . After 8 weeks of treatment with one of the drugs , the other treatment was given for 8 weeks . The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring , measurement of large artery stiffness , and neurohormonal plasma levels at baseline and after 8 weeks of either treatment . Sixteen patients ( mean age 37 + /- 12 years , 26 + /- 15 years after repair , 63 % men ) completed the study . The 24-hour mean arterial pressure at baseline was 97.7 + /- 6.2 mm Hg . Metoprolol ( mean dose 163 + /- 50 mg/day ) decreased the mean arterial pressure ( 7.0 + /- 4.2 and 4.1 + /- 3.6 mm Hg , respectively ) more than did c and esartan ( mean dose 13 + /- 4 mg/day ; p = 0.018 , 95 % confidence interval 0.6 to 5.5 ) . Large artery stiffness did not change with either treatment . With metoprolol , plasma B-type natriuretic peptide increased and plasma renin decreased . With c and esartan , the plasma renin and noradrenaline levels increased and aldosterone levels decreased . In conclusion , in adult hypertensive patients after CoA repair , metoprolol had more of an antihypertensive effect than did c and esartan . Moreover , the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after AIMS This study quantified hypertension load using 24-h ambulatory blood pressure monitoring after successful repair of coa rct ation of the aorta less than ( 1 ) or more than 10 years previously ( 2 ) and examined the influence of the surgical procedure ( anastomosis or subclavian flap ) . METHODS AND RESULTS Ambulatory blood pressure recordings were obtained using an Accutracker II monitor every 30 min during the day and hourly , at night . Day and night systolic and diastolic values were higher in coa rct ation of the aorta than in controls : ( day : systolic blood pressure/diastolic blood pressure : 133/71 + /- 6/4 vs 115/66 + /- 3/2 night : systolic blood pressure/diastolic blood pressure : 117/61 + /- 4/4 vs 107/57 + /- 3/2 mmHg , P < 0.01 ) and at all times , were higher in coa rct ation of the aorta ( 2 ) than in coa rct ation of the aorta ( 1 ) . Clinical daytime systolic hypertension was observed in 20 % of recordings from coa rct ation of the aorta ( 1 ) and 49 % from coa rct ation of the aorta ( 2 ) while diastolic hypertension was not observed . However , systolic blood pressure and diastolic blood pressure responses to daily activities were significantly higher in coa rct ation of the aorta than in controls and this was more marked in coa rct ation of the aorta ( 2 ) than in coa rct ation of the aorta ( 1 ) . Type of surgery did not affect either hypertension prevalence or blood pressure reactivity . CONCLUSIONS These observations indicate exaggerated systolic blood pressure and diastolic blood pressure reactivity after repair of coa rct ation of the aorta , the prevalence of systolic hypertension doubling 10 years after surgery |
471 | 25,660,427 | In terms of efficacy , there is considerable heterogeneity among the studies , and no conclusive results were found concerning the superiority of the hypofractionated option over the normal fractionated option .
In terms of safety , there were no significant differences in the onset of acute genitourinary complications between the 2 treatments .
There were no significant differences in long-term complications based on the type of radiation therapy used , although the studies did have limitations .
To date , there are no conclusive results that show that hypofractionated radiation therapy is more effective or safer than normal fractionated radiation therapy in the treatment of localized prostate cancer | CONTEXT New therapeutic alternatives can improve the safety and efficacy of prostate cancer treatment .
OBJECTIVES To assess whether hypofractionated radiation therapy results in better safety and efficacy in the treatment of prostate cancer . | PURPOSE To assess in a prospect i ve trial the feasibility and late toxicity of hypofractionated radiotherapy ( RT ) for prostate cancer . METHODS AND MATERIAL S Eligible patients had clinical stage T1c-2cNXM0 disease . They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers . RESULTS Between June 2001 and March 2004 , 92 patients were treated with hypofractionated RT . The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5 - 6 ( 38 % ) or 7 ( 59 % ) disease , and 82 patients had T1c-T2a clinical staging . Overall , 29 patients had low-risk , 56 intermediate-risk , and 7 high-risk disease . Severe acute toxicity ( Grade 3 - 4 ) was rare , occurring in only 1 patient . Median follow-up was 38 months . According to the Phoenix definition for biochemical failure , the rate of biochemical control at 14 months was 97 % . According to the previous American Society for Therapeutic Radiology and Oncology definition , biochemical control at 3 years was 76 % . The incidence of late toxicity was low , with no severe ( Grade > or =3 ) toxicity at the most recent assessment . CONCLUSIONS Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity . At early follow-up , biochemical outcome is comparable to that reported for conventionally fractionated controls . The findings are being tested in an ongoing , multicenter , Phase III trial PURPOSE To compare the toxicity and efficacy of hypofractionated ( 62 Gy/20 fractions/5 weeks , 4 fractions per week ) vs. conventional fractionation radiotherapy ( 80 Gy/40 fractions/8 weeks ) in patients with high-risk prostate cancer . METHODS AND MATERIAL S From January 2003 to December 2007 , 168 patients were r and omized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles . All patients received a 9-month course of total and rogen deprivation ( TAD ) , and radiotherapy started 2 months thereafter . RESULTS The median ( range ) follow-up was 32 ( 8 - 66 ) and 35 ( 7 - 64 ) months in the hypofractionation and conventional fractionation arms , respectively . No difference was found for late toxicity between the two treatment groups , with 3-year Grade 2 rates of 17 % and 16 % for gastrointestinal and 14 % and 11 % for genitourinary in the hypofractionation and conventional fractionation groups , respectively . The 3-year freedom from biochemical failure ( FFBF ) rates were 87 % and 79 % in the hypofractionation and conventional fractionation groups , respectively ( p = 0.035 ) . The 3-year FFBF rates in patients at a very high risk ( i.e. , pretreatment prostate-specific antigen ( iPSA ) > 20 ng/mL , Gleason score > or=8 , or T > or=2c ) , were 88 % and 76 % ( p = 0.014 ) in the former and latter arm , respectively . The multivariate Cox analysis confirmed fractionation , iPSA , and Gleason score as significant prognostic factors . CONCLUSIONS Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF PURPOSE The aim of this study was to compare the toxicity and efficacy of radiation therapy ( RT ) for localized carcinoma of the prostate , using a hypofractionated ( 55 Gy/20 fractions/4 weeks ) vs. a conventionally fractionated ( 64 Gy/32 fractions/6.5 weeks ) dose schedule . METHODS AND MATERIAL S A total of 217 patients were r and omized to either the hypofractionated ( 108 patients ) or the conventional ( 109 patients ) dose schedule , with planning with two-dimensional ( 2D ) CT scan planning methodology in the majority of cases . All patients were followed for a median of 48 ( 6 - 108 ) months . Gastrointestinal ( GI ) and genitourinary ( GU ) toxicity was evaluated before RT and after its completion using modified late effects of normal tissue-subjective , objective , management , analytic ( LENT-SOMA ) scales and the European Organization for Research and Treatment of Cancer sexual function question naire . Efficacy of RT based on clinical , radiologic , and prostate-specific antigen data were also evaluated at baseline and after RT . RESULTS Gastrointestinal and GU toxicity persisted 5 years after RT and did not differ between the two dose schedules other than in regard to urgency of defecation . However , 1-month GI toxicity was not only worse in patients with the hypofractionated RT schedule but also adversely affected daily activities . Nadir prostate-specific antigen values occurred at a median of 18.0 ( 3.0 - 54.0 ) months after RT . A total of 76 biochemical relapses , with or without clinical relapses , have occurred since ; of these , 37 were in the hypofractionated and 39 in the conventional schedule . The 5-year biochemical + /- clinical relapse-free and overall survival was 55.9 % and 85.3 % respectively for all patients , and did not differ between the two schedules . CONCLUSIONS Radiation therapy for prostate carcinoma causes persistent GI toxicity that is largely independent of the two dose schedules . The hypofractionated schedule is equivalent in efficacy to the conventional schedule Purpose To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule ( C-ARM ) with 78 Gy/39 fractions and hypofractionation conformal treatment ( H-ARM ) with 69 Gy/23 fractions . Methods and material This prospect i ve double arm study consisted of 217 patients with prostate cancer , 112 in H-ARM and 105 in C-ARM arm . C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions . Weekly assessment of acute reactions was done during treatment and with one , and 3 months using RTOG scale . Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms . Variables with p value less than 0.1 were included in the multivariated logistic regression . Results There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary ( GU ) and gastrointestinal ( GI ) acute toxicity . During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity ( grade 0–3 ; H-ARM = 45.5 % , 34 % , 18.7 % and 1.8 % versus C-ARM = 47.6 % , 35.2 % , 17.2 % and 0 ) . For acute GU toxicity no difference was detected between H-ARM ( grade 0–3 ; 22.3 % , 54.5 % , 18.7 % and 4.5 % ) and C-ARM ( grade 0–3 ; 25.8 % , 53.3 % , 17.1 % and 3.8%).At the 3- months follow-up , persistent Grade > = 2 acute GU and GI toxicity were 2.5 % and 1.8 % in H-ARM versus 5.7 % and 3 % in C-ARM ( p > 0.05 ) . In univariated and multivariated analyses , there was not any dosimetric predictor for GI and GU toxicity . Conclusions Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer , being well tolerated with minimal severe acute toxicity OBJECTIVE To report late toxicity outcomes from a r and omized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment . METHODS AND MATERIAL S Men with localized prostate cancer were enrolled in a trial that r and omized men to either conventionally fractionated intensity modulated radiation therapy ( CIMRT , 75.6 Gy in 1.8-Gy fractions ) or to dose-escalated hypofractionated IMRT ( HIMRT , 72 Gy in 2.4-Gy fractions ) . Late ( ≥90 days after completion of radiation therapy ) genitourinary ( GU ) and gastrointestinal ( GI ) toxicity were prospect ively evaluated and scored according to modified Radiation Therapy Oncology Group criteria . RESULTS 101 men received CIMRT and 102 men received HIMRT . The median age was 68 , and the median follow-up time was 6.0 years . Twenty-eight percent had low-risk , 71 % had intermediate-risk , and 1 % had high-risk disease . There was no difference in late GU toxicity in men treated with CIMRT and HIMRT . The actuarial 5-year grade ≥2 GU toxicity was 16.5 % after CIMRT and 15.8 % after HIMRT ( P=.97 ) . There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT . The actuarial 5-year grade ≥2 GI toxicity was 5.1 % after CIMRT and 10.0 % after HIMRT ( P=.11 ) . In men receiving HIMRT , the proportion of rectum receiving 36.9 Gy , 46.2 Gy , 64.6 Gy , and 73.9 Gy was associated with the development of late GI toxicity ( P<.05 ) . The 5-year actuarial grade ≥2 GI toxicity was 27.3 % in men with R64.6Gy ≥ 20 % but only 6.0 % in men with R64.6Gy < 20 % ( P=.016 ) . CONCLUSIONS Dose-escalated IMRT using a moderate hypofractionation regimen ( 72 Gy in 2.4-Gy fractions ) can be delivered safely with limited grade 2 or 3 late toxicity . Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen Purpose : To compare acute gastrointestinal ( GI ) and genitourinary ( GU ) toxicity between patient groups with localized prostate adenocarcinoma , treated with conventionally fractionated ( CFRT ) and hypofractionated ( HFRT ) three-dimensional conformal external-beam radiotherapy ( 3D-CRT ) . Patients and Methods : 91 patients were enrolled into a r and omized study with a minimum follow-up of 3 months . 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks . 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks , given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy . The clinical target volume ( CTV ) included the prostate and the base of seminal vesicles . The CTV-to-PTV ( planning target volume ) margin was 8–10 mm . Study patients had portal imaging and /or simulation performed on the first fractions and repeated at least weekly . Results : No acute grade 3 or 4 toxicities were observed . The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm : 19.1 % versus 47.7 % ( χ2-test , p = 0.003 ) . The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm ( log-rank test , p = 0.008 ) . The median duration of overall GI acute toxicity was shorter with HFRT : 3 compared to 6 weeks with CFRT ( median test , p = 0.017 ) . Conclusion : In this first evaluation , the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule . Extended follow-up is needed to justify this fractionation schedule ’s safety in the long term . Ziel : Es soll die Frage beantwortet werden , ob bei der Beh and lung des lokalisierten Adenokarzinoms der Prostata ein hypofraktioniertes Schema ( HFRT ) die gleichen Tumorkontroll- und Nebenwirkungsraten zeigt wie ein konventionelles Schema ( CFRT ) . Hier wird uber die ersten Ergebnisse zu den Nebenwirkungen berichtet . Patienten und Method ik:91 Patienten wurden i m Rahmen einer Studie r and omisiert beh and elt , die minimale Nachbeobachtungszeit lag bei 3 Monaten . I m CFRT-Arm ( 44 Patienten ) betrug die Dosis 74 Gy ( 37 × 2 Gy/d ) , i m HFRT-Arm ( 47 Patienten ) 57 Gy ( 17 × 3 Gy/d , 4 × 4,5 Gy/d ) . Das klinische Zielvolumen ( CTV ) umfasste die Prostata und die Basis der Samenblaschen , der Sicherheitsr and um das CTV betrug 8–10 mm . Verifikationsaufnahmen ( EPI [ " electronic portal imaging " ] ) wurden zu Beginn der Beh and lung und danach wochentlich angefertigt . Ergebnisse : Nebenwirkungen der Grade 3 und 4 wurden nicht beobachtet . Die Rate an urologischen Grad-2-Nebenwirkungen war fur die HFRT mit 19,1 % i m Vergleich zu 47,7 % bei der CFRT signifikant geringer ( χ2-Test , p = 0,003 ) . Auserdem traten die Grad-2-Nebenwirkungen i m HFRT-Arm deutlich spater auf als i m CFRT-Arm ( Log-Rank-Test , p = 0,008 ) . Gastrointestinale Grad-2-Nebenwirkungen hielten bei der HFRT i m Median 3 Wochen , bei der CFRT 6 Wochen an ( Mediantest , p = 0,017).Schlussfolgerung : In der ersten Auswertung zeigen sich Vorteile fur das HRFT-Schema in Bezug auf die Frequenz und die Dauer der Grad-2-Toxizitaten . Es ist aber eine langere Nachbeobachtungszeit notwendig , um dieses Schema als sicher akzeptieren zu konnen PURPOSE To estimate the late morbidity of a novel , hypofractionated external beam radiotherapy schedule of 55 Gy in 16 fractions ( 4 fractions/week , 3.4 Gy per fraction ) for localized prostate cancer . METHODS AND MATERIAL S A multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006 . After insertion of fiducial gold markers , they were treated with image-guidance ( IGRT ) using conformal techniques with intensity-modulation , if necessary , and then followed every 6 months for toxicity rating and PSA . Patient reported outcomes were collected yearly . Median follow up was 4.6 years . RESULTS At 4 years post-radiotherapy , the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7 % ( 95 % CI 3 - 16 % ) and grade 2 + was 33 % ( 95 % CI 24 - 46 % ) . All except two patients recovered from their grade 3 events . Patient-reported reduction of function was most pronounced at year two for urinary function ( mean -7 , SD 16 ) , and at year one for bowel function ( mean -7 , SD 21 ) . The cumulative incidence of biochemical ( PSA nadir+2 ) or biopsy-proven relapse at 4 years was 9 % ( 95 % CI 4 - 18 % ) . CONCLUSIONS Hypofractionated radiotherapy is clinical ly feasible and more convenient than conventional schedules for patients with localized prostate cancer . Phase 3 multicenter studies are on-going ( NCT00126165 ) PURPOSE To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy ( SHARP ) for localized prostate cancer . METHODS AND MATERIAL S A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions , calculated to be biologically equivalent to 78 Gy in 2 Gy fractions ( alpha/beta ratio of 1.5 Gy ) . Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment . Genitourinary ( GU ) and gastrointestinal ( GI ) toxicity were evaluated by American Urologic Association ( AUA ) score and Common Toxicity Criteria ( CTC ) . Prostate-specific antigen ( PSA ) values and self-reported sexual function were recorded at specified follow-up intervals . RESULTS The study includes 40 patients . The median follow-up is 41 months ( range , 21 - 60 months ) . Acute toxicity Grade 1 - 2 was 48.5 % ( GU ) and 39 % ( GI ) ; 1 acute Grade 3 GU toxicity . Late Grade 1 - 2 toxicity was 45 % ( GU ) and 37 % ( GI ) . No late Grade 3 or higher toxicity was reported . Twenty-six patients reported potency before therapy ; 6 ( 23 % ) have developed impotence . Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70 % for the American Society for Therapeutic Radiology and Oncology definition and 90 % by the alternative nadir + 2 ng/mL failure definition . CONCLUSIONS SHARP for localized prostate cancer is feasible with minimal acute or late toxicity . Dose escalation should be possible PURPOSE To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy ( IMRT ) . METHODS AND MATERIAL S Between 2003 and 2006 , 82 prostate cancer patients with a nodal involvement risk ≤20 % ( Roach index ) have been treated to the prostate with or without seminal vesicles with 56 Gy ( 4 Gy/fraction twice weekly ) and an overall treatment time of 6.5 weeks . Acute and late genitourinary ( GU ) and gastrointestinal ( GI ) toxicities were scored according to the Radiation Therapy Oncology Group ( RTOG ) grading system . Median follow-up was 48 months ( range , 9 - 67 months ) . RESULTS All patients completed the treatment without interruptions . No patient presented with Grade ≥3 acute GU or GI toxicity . Of the patients , 4 % presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion . The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2 % ± 2.9 % and 96.1 % ± 2.2 % , respectively . One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity , which were transitory in both cases . The 4-year actuarial biochemical relapse-free survival was 91.3 % ± 5.9 % , 76.4 % ± 8.8 % , and 77.5 % ± 8.9 % for low- , intermediate- , and high-risk groups , respectively . CONCLUSIONS In patients with localized prostate cancer , acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy , with IMRT . Further prospect i ve trials are warranted to further assess the best fractionation schemes for these patients PURPOSE To evaluate the long-term efficacy and toxicity of a hypofractionated ( 55 Gy in 20 fractions within 4 weeks ) vs. a conventionally fractionated ( 64 Gy in 32 fractions within 6.5 weeks ) dose schedule for radiotherapy ( RT ) for localized carcinoma of the prostate . METHODS AND MATERIAL S A total of 217 patients were r and omized to either the hypofractionated ( n=108 ) or the conventional ( n=109 ) dose schedule . Most patients ( n=156 ) underwent RT planning and RT using a two-dimensional computed tomography method . Efficacy using the clinical , radiologic , and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death . Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue-Subjective Objective Management Analytic ( LENT-SOMA ) scales was also evaluated before and at intervals after RT to 60 months . RESULTS The whole group has now been followed for a median of 90 months ( range , 3 - 138 ) . Of the 217 patients , 85 developed biochemical relapse ( nadir prostate-specific antigen level+2 μg/L ) , 36 in the hypofractionated and 49 in the conventional group . The biochemical relapse-free , but not overall , survival at 90 months was significantly better with the hypofractionated ( 53 % ) than with the conventional ( 34 % ) schedule . Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules . Multivariate analyses revealed that the conventional schedule was of independent prognostic significance , not only for biochemical failure , but also for an increased risk of worse genitourinary symptoms at 4 years . CONCLUSIONS A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study PURPOSE We performed a r and omized trial to compare the GI and urogenital toxicity of radiotherapy ( RT ) for localized ( confined to the organ ) , early-stage ( T1-T2N0M0 , TNM classification ) carcinoma of the prostate , using a conventional ( 64 Gy in 32 fractions within 6.5 weeks ) vs. a hypofractionated ( 55 Gy in 20 fractions within 4 weeks ) schedule and to determine the efficacy of the respective treatment schedules . METHODS AND MATERIAL S This report is based on an interim analysis of the first 120 consecutive patients in this Phase III trial after a median follow-up of 43.5 months ( range 23 - 62 ) . RT planning was based on two-dimensional CT data , and the treatment was delivered using a three- or four-field 6 - 23-MV photon technique . GI and urogenital toxicity ( symptom question naires incorporating the subjective elements of the late effects of normal tissues-subjective , objective , management , analytic classification of late effects and the European Organization for Research and Treatment of Cancer sexual function question naire ) were evaluated before RT and 1 month , 1 year , and 2 years after RT completion . The efficacy of RT was assessed clinical ly ( digital rectal examination and radiologic imaging ) and biochemically ( prostate-specific antigen assay ) at baseline , and every 3 months for 2 years after RT and every 6 months subsequently . RESULTS RT , whether conventional or hypofractionated , result ed in an increase in all six symptom categories used to characterize GI toxicity and in four of five symptom categories used to document urinary morbidity 1 month after therapy completion . Sexual dysfunction ( based on limited data ) , which existed in more than one-third of patients before RT , also increased to just more than one-half of patients 1 month after RT . The increase in urinary toxicity after RT was not sustained ( diurnal urinary frequency had decreased significantly at 2 years ) . In contrast , all six symptom categories of GI toxicity remained increased 1 year after RT . Four of the six GI symptom categories ( rectal pain , mucous discharge , urgency of defecation , and rectal bleeding ) were still increased at 2 years compared with baseline . Except for a slightly greater percentage of patients experiencing mild rectal bleeding at 2 years among those who received hypofractionated RT , no differences were noted in toxicity between the conventional and hypofractionated RT schedule . The mean prostate-specific antigen level was 14.0 + /- 1.0 ng/mL at baseline and declined to a nadir of 1.3 + /- 0.2 ng/mL at a median of 16.8 months ( range 0.8 - 28.3 ) after RT completion . However , it then rose in 17 patients ( 8 in the hypofractionated and 9 in the conventional treatment group ) . Only 8 of these 17 patients were found to have signs of clinical relapse ( 5 local , 1 regional lymph node , and 2 systemic [ bony metastases ] ) after histopathologic and radiologic re assessment ) . The remaining 9 patients had biochemical relapse only ( defined as three consecutive rises in prostate-specific antigen after nadir ) . The 4-year biochemical relapse-free survival rate was 85.8 % for all patients and did not differ significantly between the two radiation dose schedules ( 86.2 % for the hypofractionated and 85.5 % for the conventional fractionation group ) . CONCLUSION RT for prostate carcinoma , using a three- or four-field 6 - 23-MV photon technique without posterior shielding of the lateral fields , is an underestimated cause of persistent GI morbidity . The incidence of clinical ly significant GI and urogenital toxicity after conventional and hypofractionated RT appears to be similar . Hypofractionated RT for carcinoma of the prostate seems just as effective as conventional RT after a median follow-up approaching 4 years The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The |
472 | 26,928,025 | Pharmacy-based interventions produced similar weight loss compared with active interventions in other primary care setting s ; however , weight loss was not sustained longer term in a range of primary care and commercial setting s compared with control .
Pharmacy-based weight management interventions have similar provider costs to those delivered in other primary care setting s , which are greater than those delivered by commercial organisations .
Very few studies explored if and how sociodemographic or socioeconomic variables moderated intervention effects .
Insufficient information was available to examine relationships between effectiveness and behaviour change strategies , implementation factors , or organisation and delivery of interventions .
Community pharmacy-delivered interventions are effective for smoking cessation , and demonstrate that the pharmacy is a feasible option for weight management interventions . | OBJECTIVES To systematic ally review the effectiveness of community pharmacy-delivered interventions for alcohol reduction , smoking cessation and weight management . | BACKGROUND AND AIMS To undertake the first r and omized controlled trial to evaluate the effectiveness of a brief intervention delivered by community pharmacists to reduce hazardous or harmful drinking . DESIGN This parallel group r and omized trial allocated participants individually to brief alcohol intervention ( n = 205 ) or a leaflet-only control condition ( n = 202 ) , with follow-up study after 3 months . SETTING Sixteen community pharmacies in one London Borough , UK . PARTICIPANTS A total of 407 pharmacy customers ( aged 18 years or over ) with Alcohol Use Disorder Identification Test ( AUDIT ) scores 8 - 19 , inclusive . INTERVENTION A brief motivational discussion of approximately 10 minutes ' duration , for which 17 pharmacists received a half-day of training . MEASUREMENTS Hazardous or harmful drinking was assessed using the AUDIT administered by telephone by a research er blind to allocation status . The two primary outcomes were : ( 1 ) change in AUDIT total scores and ( 2 ) the proportions no longer hazardous or harmful drinkers ( scoring < 8) at 3 months . The four secondary outcomes were : the three subscale scores of the AUDIT ( for consumption , problems and dependence ) and health status according to the EQ-5D ( a st and ardized instrument for use as a measure of health outcome ) . FINDINGS At 3 months 326 ( 80 % overall ; 82 % intervention , 78 % control ) participants were followed-up . The difference in reduction in total AUDIT score ( intervention minus control ) was -0.57 , 95 % confidence interval ( CI ) = -1.59 to 0.45 , P = 0.28 . The odds ratio for AUDIT ˂ 8 ( control as reference ) was 0.87 , 95 % CI = 0.50 to 1.51 , P = 0.61 ) . For two of the four secondary outcomes ( dependence score : -0.46 , 95 % CI = -0.82 to -0.09 , P = 0.014 ; health status score : -0.09 , 95 % CI = -0.16 to -0.02 , P = 0.013 ) the control group did better , and in the other two there were no differences ( consumption score : -0.05 , 95 % CI = -0.54 to 0.44 , P = 0.85 ; non-dependence problems score : -0.13 , 95 % CI = -0.66 to 0.41 ) . Sensitivity analyses did not change these findings . CONCLUSIONS A brief intervention delivered by community pharmacists appears to have had no effect in reducing hazardous or harmful alcohol consumption OBJECTIVE To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model . DESIGN A r and omised controlled trial of community pharmacies and pharmacy customers . SETTING All 76 non-city community pharmacies registered in Grampian , Scotl and , were invited to participate . Sixty-two pharmacies ( 82 % ) were recruited . SUBJECTS All the intervention pharmacy personnel were invited to attend the training ; 40 pharmacists and 54 assistants attended . A total of 492 customers who smoked ( 224 intervention , 268 controls ) were recruited during the 12-month recruitment period ( overall recruitment rate 63 % ) . MAIN OUTCOME MEASURES The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one , four , and nine months . RESULTS The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel , 85 % ( 113 ) compared with 62 % ( 99 ) of the controls ( p<0.001 ) . The former also rated their discussion more highly ; 34 % ( 45 ) of the intervention customers compared with 16 % ( 25 ) of the controls rated it as “ very useful ” ( p = 0.048 ) . Assuming non-responders had lapsed , one-month point prevalence of abstinence was cl aim ed by 30 % of intervention customers and 24 % of controls ( p = 0.12 ) ; four months ’ continuous abstinence was cl aim ed by 16 % of intervention customers and 11 % of controls ( p = 0.094 ) ; and nine months ’ continuous abstinence was cl aim ed by 12 % of intervention customers and 7 % of controls ( p = 0.089 ) . These trends in outcome were not affected by potential confounders ( sex , age , socioeconomic status , nicotine dependence , and type of nicotine replacement product used ) or adjustment for clustering . CONCLUSIONS The intervention was associated with increased and more highly rated counselling , and a trend toward higher smoking cessation rates , indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets Background Tobacco smoking leads to death or disability and a drain on national re sources . The literature suggests that cigarette smoking continues to be a major modifiable risk factor for a variety of diseases and that smokers aged 18 - 30 years are relatively resistant to antismoking messages due to their widely held belief that they will not be lifelong smokers . Objective To conduct a r and omized controlled trial ( RCT ) of a computer-generated photoaging intervention to promote smoking cessation among young adult smokers within a community pharmacy setting . Methods A trial was design ed with 80 % power based on the effect size observed in a published pilot study ; 160 subjects were recruited ( 80 allocated to the control group and 80 to the intervention group ) from 8 metropolitan community pharmacies located around Perth city center in Western Australia . All participants received st and ardized smoking cessation advice . The intervention group participants were also digitally photoaged by using the Internet-based APRIL Face Aging software so they could p review images of themselves as a lifelong smoker and as a nonsmoker . Due to the nature of the intervention , the participants and research er could not be blinded to the study . The main outcome measure was quit attempts at 6-month follow-up , both self-reported and biochemically vali date d through testing for carbon monoxide ( CO ) , and nicotine dependence assessed via the Fagerström scale . Results At 6-month follow-up , 5 of 80 control group participants ( 6.3 % ) suggested they had quit smoking , but only 1 of 80 control group participants ( 1.3 % ) consented to , and was confirmed by , CO validation . In the intervention group , 22 of 80 participants ( 27.5 % ) reported quitting , with 11 of 80 participants ( 13.8 % ) confirmed by CO testing . This difference in biochemically confirmed quit attempts was statistically significant ( χ2 1=9.0 , P=.003 ) . A repeated measures analysis suggested the average intervention group smoking dependence score had also significantly dropped compared to control participants ( P<.001 ) . These differences remained statistically significant after adjustment for small differences in gender distribution and nicotine dependence between the groups . The mean cost of implementing the intervention was estimated at AU $ 5.79 per participant . The incremental cost-effectiveness ratio was AU $ 46 per additional quitter . The mean cost that participants indicated they were willing to pay for the digital aging service was AU $ 20.25 ( SD 15.32 ) . Conclusions Demonstrating the detrimental effects on facial physical appearance by using a computer-generated simulation may be both effective and cost-effective at persuading young adult smokers to quit . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12609000885291 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12609000885291 ( Archived by WebCite at http://www.webcitation.org/6F2kMt3kC OBJECTIVE To compare a meal replacement ( MR ) program with a conventional reduced-calorie diet ( RCD ) for weight management using the pharmacy as the setting and the pharmacist as the point of contact for dietary advice . DESIGN R and omized , controlled , open-label trial . SETTING Travis Pharmacy in Shen and oah , Iowa . PATIENTS Ninety-five patients from southwestern iowa and southeastern Nebraska were enrolled , of whom 88 were considered eligible for comparison ( by continuing through week 2 of the study ) . INTERVENTION Patients were r and omized to an MR plan or a traditional RCD plan . Patients were followed for a 3-month period of active weight loss and a 10-week period of weight maintenance . Patients returned every 3 weeks for follow-up with the pharmacist , for a total of 13 visits . MAIN OUTCOME MEASURE Weight changes . RESULTS During the active weight loss phase , the MR ( n = 45 ) and RCD ( n = 43 ) groups lost a significant amount of weight , although no significant difference was found between the groups ( mean + /- st and ard error = 4.90 + /- 0.30 kg MR versus 4.30 + /- 0.30 kg RCD ; P = .16 ) . In the weight maintenance phase , the MR group lost 0.70 + /- 0.40 kg and the RCD group lost 0.90 + /- 0.40 kg ( P = .60 ) . Significant improvements were observed in waist circumference , systolic and diastolic blood pressure , and triglyceride levels . No significant changes were seen in high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels in either group . CONCLUSION Successful weight management can be achieved in a pharmacy setting . Both MR and RCD programs were effective We conducted a r and omized , controlled study to evaluate whether pharmacists ' advice on smoking cessation would result in a higher smoking cessation rate using Nicorette ( nicotine gum preparation ) . Fourteen pharmacies in Tokyo , Kanagawa , and Nagano participated . Smokers who visited pharmacies to buy Nicorette from March 1 , 2002 , through August 31 , 2002 , were recruited and r and omly assigned to two groups . For the intervention group ( A ) , pharmacists provided both regular instructions on Nicorette use and smoking cessation advice at the first sale and then gave follow-up advice just before starting a cessation and 1 , 3 , and 8 weeks and 3 months thereafter . For the control group ( B ) , pharmacists provided regular instructions alone . The primary outcome measure was the self-reported smoking cessation rate and the secondary outcome measure was the relationship between the smoker 's egogram and effectiveness of intervention . Twenty-eight smokers were enrolled and r and omized into group A ( n=11 ) or group B ( n=17 ) . The absolute abstinence rate in groups A and B at 3 months was 45.5 % and 31.2 % , respectively . The odds ratio was 1.83 , which was not statistically significant . There was no difference in egogram score between absolute abstinence subjects and nonabstinence subjects in group A. The egogram scores in Adapted Child of absolute abstinence subjects in group B were significantly higher than in nonabstinence subjects . In conclusion , instructions and advice given by pharmacists may improve the smoking cessation rate in smokers receiving nicotine replacement therapy Background Community pharmacists can deliver health care advice at an opportunistic level , related to prescription or non-prescription medicines and as part of focused services design ed to reduce specific risks to health . Obesity , smoking and excessive alcohol intake are three of the most significant modifiable risk factors for morbidity and mortality in the UK , and interventions led by community pharmacists , aim ed at these three risk factors , have been identified by the government as public health priorities . In 2008 , the Department of Health for Engl and stated that ‘ a sound evidence base that demonstrates how pharmacy delivers effective , high quality and value for money services is needed ’ ; this systematic review aims to respond to this requirement . Methods / design We will search the data bases MEDLINE , Embase , CINAHL , PsycINFO , Social Sciences Citation Index , ASSIA , IBSS , Sociological Abstract s , Scopus and NHS Economic Evaluation Data base for studies that have evaluated interventions based on community pharmacies that aim to target weight management , smoking cessation and alcohol misuse . We will include all r and omised controlled trials ( RCTs ) , non-r and omised controlled trials ( N RCTs ) , controlled before-after studies ( CBAs ) and interrupted time series ( ITS ) and repeated measures studies . Data from included studies will be extracted by two independent review ers and will include study details methods , results , intervention implementation/costs and method ological quality . Meta- analysis will be conducted if appropriate ; if not , the synthesis will be restricted to a narrative overview of individual studies looking at the same question . Discussion The review aims to summarise the evidence base on the effectiveness of community pharmacy interventions on health and health behaviours in relation to weight management , smoking cessation and alcohol misuse . It will also explore if , and how , socio-economic status , gender , ethnicity and age moderate the effect of the interventions and will describe how the interventions included in the review have been organised , implemented and delivered , since context is an important factor governing the success of public health interventions . The findings from this review will have an impact on the commissioning of public health services aim ing to promote healthy weight , smoking cessation and prevent excessive alcohol consumption . Systematic review registration The review has been registered with PROSPERO ( registration no. CRD42013005943 ) . Available at : http://www.crd.york.ac.uk/ prospero /display_record.asp?ID = CRD42013005943 Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss . Design Eight arm r and omised controlled trial . Setting Primary care trust in Birmingham , Engl and . Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records . Interventions Weight loss programmes of 12 weeks ’ duration : Weight Watchers ; Slimming World ; Rosemary Conley ; group based , dietetics led programme ; general practice one to one counselling ; pharmacy led one to one counselling ; choice of any of the six programmes . The comparator group was provided with 12 vouchers enabling free entrance to a local leisure ( fitness ) centre . Main outcome measures The primary outcome was weight loss at programme end ( 12 weeks ) . Secondary outcomes were weight loss at one year , self reported physical activity , and percentage weight loss at programme end and one year . Results Follow-up data were available for 658 ( 88.9 % ) participants at programme end and 522 ( 70.5 % ) at one year . All programmes achieved significant weight loss from baseline to programme end ( range 1.37 kg ( general practice ) to 4.43 kg ( Weight Watchers ) ) , and all except general practice and pharmacy provision result ed in significant weight loss at one year . At one year , only the Weight Watchers group had significantly greater weight loss than did the comparator group ( 2.5 ( 95 % confidence interval 0.8 to 4.2 ) kg greater loss , ) . The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end ( mean difference 2.3 ( 1.3 to 3.4 ) kg ) . The primary care programmes were the most costly to provide . Participants allocated to the choice arm did not have better outcomes than those r and omly allocated to a programme . Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff , which are ineffective . Trial registration Current Controlled Trials IS RCT N25072883 BACKGROUND : Inappropriate use of medications is a significant problem in health care today . A possible solution to this problem may be achieved through better control of patients ' drug therapy . OBJECTIVE : To design a pharmaceutical care program for dyslipidemic patients within a community pharmacy setting that provides education in the areas of medication compliance and lifestyle modifications , while emphasizing the importance of achieving cholesterol goals to ensure improvement in quality of life . METHODS : Patients at an outpatient pharmacy volunteered to be surveyed for 16 weeks . Although both the intervention and control groups were surveyed , the r and omly selected intervention group was interviewed more frequently and more comprehensively . Cholesterol , triglycerides , glucose , weight , risk factors , drug-related problems ( DRPs ) , and quality of life were measured via a survey at the onset of the study and continually measured until the study 's conclusion . RESULTS : In the intervention group , 26 DRPs were detected , of which 24 were resolved ; in the control group , 26 DRPs were detected , of which 5 were resolved . When comparing initial and final blood cholesterol levels in the intervention group , the mean decrease was 27.0 ± 41.1 mg/dL ( p = 0.0266 ) ; in the control group , the average blood cholesterol level decreased by a mean of 1.4 ± 37.2 mg/dL ( p = 0.6624 ) . In the intervention group , the triglyceride level decreased an average of 50.5 ± 80.3 mg/dL ( p = 0.0169 ) , while the control group experienced a mean triglyceride level increase of 29.6 ± 118.5 mg/dL ( p = 0.1435 ) . As a result of the intervention , the quality of life in the intervention group was improved . CONCLUSIONS : Short-term pharmaceutical care plans developed in a retail pharmacy within the proper setting may contribute to improved blood lipid values , cardiovascular disease risk factors , and patients ' quality of life Objective To evaluate the effects of pharmacotherapy follow-up ( PF ) on metabolic control and clinical outcomes in type 2 diabetic patients . Setting Six community pharmacies ( 4 intervention and 2 control ) in the Curitiba metropolitan region ( Brazil ) . Main outcome measure Glycosylated Haemoglobin A1 ( HbA1 ) and fasting capillary glycaemia . Methods We conducted a 12-month controlled trial involving a total of 161 patients in six community pharmacies between July 2004 and March 2006 . Pharmacotherapy follow-up was applied only to patients in the intervention group . Results Of the 161 patients enrolled , 96 completed the study ( 50 intervention and 46 control ) . The administration of 574 consultations with the intervention group patients led to 119 negative clinical outcomes ( 2.3/patient [ SD = 1.6 ] ) . The majority of detected problems were related to the ineffectiveness of pharmacotherapy ( 68.1 % ) . Relative to the control group , the intervention group exhibited greater glycosylated haemoglobin ( HbA1 ) reduction ( −2.2 % [ 95%CI −2.8%:−1.6 % ] vs. −0.3 [ 95 % CI −0.8:0.2 ] ; P < 0.001 ) and greater fasting capillary glycaemia reduction ( −20.1 mg/dl [ 95 % CI −31.9 mg/dl:−8.3 mg/dl ] vs. 4.3 mg/dl [ 95 % CI −13.4 mg/dl:22.2 mg/dl ] ; P = 0.022 ) . These differences persisted after adjustment for baseline values . There were no significant differences in any other clinical measures between the groups . There were also no significant changes in the number of medications and treatment regimens between groups , with the exception of the percentage of patients undergoing lipid lowering treatment , which increased in the intervention group from 16 % to 24 % ( P = 0.018 ) . The initial medication regimen complexity index ( MRCI ) in the intervention group was 15.5 ( SD = 7.8 , range 4–40.5 ) , and it decreased by 1.2 units ( SD = 5.9 ) after 12 months ( P = 0.149 ) . Conclusions PF of type 2 diabetic patients in community pharmacies can improve the glycaemia control of patients through optimisation of medication profiles without significant changes in either the number of drugs used or the regimen complexity Pharmacists may be effective health care practitioners to deliver smoking cessation interventions . This paper examines the short-term outcomes of smokers r and omized to one of two models of a pharmacist-led smoking cessation intervention . Methods : An open-label pragmatic r and omized trial compared two models of a pharmacist-led behavioral intervention [ Group A ( 3-sessions ) vs. Group B ( 1-session ) ] in conjunction with 5 weeks of nicotine replacement therapy ( NRT ) . Ninety-eight pharmacies in Ontario , Canada delivered the intervention . Baseline demographic and smoking behavior data were recorded , as were intervention characteristics . Self-reported , 7-day point prevalence quit rates were obtained 5-week postintervention start date . Results : 6,987 individuals participated ; 51.4 % ( n = 3588 ) r and omized to Group A ; 48.6 % ( n = 3399 ) to Group B. Approximately , 50 % of Group A participants completed all three sessions . Quit rates were significantly higher among Group A , 3-session completers ( 27.7 % ; n = 478 ) compared to Group B participants ( 18.0 % ; n = 604 ) . Multivariable results suggest that even when controlling for possible confounders and clustering across pharmacies , Group A participants who completed all three sessions were more likely to quit compared to Group B [ OR = 1.72 ( 95 % CI : 1.53 , 1.94 ) ] . Conclusions : Cessation outcomes are higher among participants completing three intervention sessions compared to one session ; however , many do not return for follow-up sessions AIMS To evaluate whether a structured community pharmacy-based smoking cessation programme ( the PAS model ) would give rise to a higher smoking cessation rate compared with ad hoc advice from pharmacists . DESIGN A r and omized controlled trial comparing a structured intervention with usual care . SETTING One hundred pharmacists working in community pharmacies in N. Irel and and 24 in London took part in the study and were each asked to enroll 12 smokers ; 44 % of pharmacists who were trained managed to recruit one or more smokers during the recruitment period of approximately 1 year . PARTICIPANTS A total of 484 smokers were enrolled by the pharmacists and individually r and omized into the PAS intervention group ( N = 265 ) or the control group ( N = 219 ) . INTERVENTION The PAS intervention involved a structured counselling programme , an information leaflet and a follow-up weekly for the first 4 weeks then monthly as needed . MEASUREMENTS The primary outcome measure of this study was self-reported smoking cessation for 12 months with cotinine validation at the 12-month follow-up . FINDINGS Of smokers in the PAS group , 14.3 % ( 38 ) were abstinent up to 12 months compared with 2.7 % ( 6 ) in the control group ( p < 0.001 for the difference ) . CONCLUSION The community pharmacy-based PAS smoking cessation service can be an effective method of helping people stop smoking when delivered by pharmacists willing to adopt this approach Objective Poor metabolic control and high associated morbidity and mortality among type 2 diabetic patients require a level of care from the pharmacist that goes beyond usual dispensing . The aim of the present study was to evaluate the improvement in metabolic control , the resolution of drug-related problems ( DRPs ) and the increase in patient awareness of diabetes as outcomes of a pharmacotherapy follow-up program in type 2 diabetic patients . Method R and omized controlled trial conducted in 14 community pharmacies in the province of Pontevedra ( Spain ) with 112 patients between February 2003 and March 2004 . The control group received the usual care , and the intervention group patients were included in a pharmacotherapy follow-up program . This individualized program , which consists of the detection and resolution of DRPs and diabetes education , involves patients in their own care in order to obtain maximum benefit from the medication they use . Main outcome measures HbA1c , Fasting Blood Glucose ( FBG ) , lipid profile , blood pressure , body mass index ( BMI ) , DRPs and knowledge were evaluated at the onset of the program and periodically until conclusion . Results There was a significant difference in changes from baseline between the intervention and the control group in DRPs ( 1.7±1.2 versus 3.1±1.2 P<0.0001 ) , knowledge ( 17.9±3.7 versus 11.4±6.7 points P<0.0001 ) , HbA1c ( 7.9±1.7 versus 8.5±1.9 % P<0.0001 ) , FBG ( 154±61.3 versus 168±57.8 mg/dl P=0.0004 ) , total cholesterol ( 202±41.5 versus 217±43.5 mg/dl P=0.0054 ) and SBP ( 135±16.4 versus 150±19.9 mmHg P=0.0006 ) . Conclusions A substantial number of patients showed an improvement in their outcomes for the chosen metabolic indicators . Pharmacotherapy follow-up programs conducted by community pharmacists can play an important role in achieving therapeutic goals in patients with type 2 diabetes . This study shows that the incorporation of type 2 diabetic patients in a pharmacotherapy follow-up program may contribute to achieve positive clinical outcomes and will contribute to the implementation and progress of pharmacotherapy follow-up programs in community pharmacies 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 The authors examined the efficacy of transdermal nicotine replacement for cessation in 410 adult nonsmoking chewing tobacco users . Participants were r and omly assigned to 6 weeks of 15-mg nicotine patch plus behavioral treatment or placebo patch plus behavioral treatment . All participants received the same behavioral treatment of 2 pharmacy visits , 2 support calls , and self-help material s. At 6 months after treatment , biochemically confirmed point-prevalence rates ( no chewing in the last 7 days ) in the active ( 38 % ) and placebo ( 34 % ) groups were high and not significantly different . The difference in relapse ( no chewing for 7 consecutive days ) between the active patch group ( 33 % ) and placebo group ( 48 % ) was significant at 6 months ( p = .003 ) . Nicotine dependence and age predicted nonrelapse at 6 months . The results suggest that nicotine replacement may improve chewers ' chances of abstinence INTRODUCTION Pharmacists are uniquely positioned within the community to provide smoking cessation counseling to their patients . However , pharmacists experience significant barriers to providing counseling , including limited time , reimbursement , and training in counseling techniques . We tested a computer-driven software system , " Exper_Quit " ( EQ ) , that provided individually tailored interventions to patients who smoke and matching tailored reports for pharmacists to help guide cessation counseling . METHODS A two-phase design was used to recruit an observation-only group ( OBS ; n = 100 ) , followed by participants ( n = 200 ) r and omly assigned to receive either EQ-assisted pharmacist counseling or EQ plus 8 weeks of nicotine transdermal patch ( EQ+ ) . Both treatment groups were scheduled to receive two follow-up counseling calls from pharmacists . RESULTS Most participants in the EQ and EQ+ groups reported receiving counseling from a pharmacist , including follow-up calls , while none of the OBS participants reported speaking with the pharmacist about cessation . At 6 months , fewer OBS participants reported a quit attempt ( 42 % ) compared with EQ ( 76 % ) or EQ+ ( 65 % ) participants ( p < .02 ) . At 6 months , 7-day point-prevalence abstinence was 28 % and 15 % among the EQ+ and EQ groups , respectively , compared with 8 % among OBS participants ( p < .01 ) , and EQ+ participants were twice as likely to be quit than were EQ participants ( p < .01 ) . DISCUSSION A tailored software system can facilitate the delivery of smoking cessation counseling to pharmacy patients . Results suggest that EQ was successful in increasing ( a ) the delivery of cessation counseling , ( b ) quit attempts , and ( c ) quit rates . Pharmacists can play an important role in the effective delivery of smoking cessation counseling The authors examined the effect of 24-hour nicotine patches in smoking cessation among over-the-counter customers in Denmark , based on a r and omized double-blind placebo-controlled trial . Participants were consecutive customers to whom nicotine patches were offered as the only treatment . Forty-two pharmacies in the areas of Aarhus and Copenhagen in Denmark participated in the trial , and 522 customers who smoked 10 or more cigarettes per day were r and omized to either nicotine patches or placebo from January to March 1994 . Customers with chronic diseases and pregnant or breastfeeding women were excluded from the trial . Twenty-four-hour patches were offered free of charge during a 3-month period . Those smoking 20 or more cigarettes per day started on a dose of 21-mg/day patches . Customers who smoked less started on patches of 14 mg/day ; and for all of the participants , the dose was gradually reduced to 7-mg/day patches during the study period . Smoking behavior and compliance were recorded by means of self-administered question naires and telephone interviews . Smoking status was recorded in intervals of 4 weeks , which was fixed to be a treatment period , and 26 weeks after inclusion . There was a significant increase in smoking cessation rates after 8 weeks of follow-up but only among smokers who started on 21-mg/day patches . There was a marked placebo effect at each time of contact during the trial , especially in those smoking fewer than 20 cigarettes per day . Although the noncompliance rate was high overall due to discontinuation in the use of patches by relapsed smokers , noncompliance among successful quitters was low . More side effects were seen in the nicotine group than in the placebo group , but none of the reported side effects were serious . It appears that regular healthy smokers who were customers of nonprescribed nicotine patches and who received 21-mg/day nicotine patches benefited from the active treatment ( 44.1 % stopped smoking after 4 weeks ) , but almost as many stopped smoking in the placebo group ( 37.3 % after 4 weeks ) . No significant differences in smoking cessation rates were seen among smokers who started with the low-dose nicotine or placebo patches |
473 | 32,010,488 | Subgroup analyses showed significant HbA1c and C-peptide improvements in patients with T1DM treated with bone marrow hematopoietic stem cells ( BM-HSCs ) , while there was no significant change in the mesenchymal stem cell ( MSC ) group .
In T2DM , HbA1c and insulin requirements decreased significantly after MSC transplantation , and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell ( BM-MNC ) treatment .
Stem cell therapy is a relatively safe and effective method for selected individuals with DM .
The data showed that BM-HSCs are superior to MSCs in the treatment of T1DM .
In T2DM , MSC and BM-MNC transplantation showed favorable therapeutic effects | Diabetes mellitus ( DM ) is a chronic metabolic disease with high morbidity and mortality .
Recently , stem cell-based therapy for DM has shown considerable promise .
Here , we undertook a systematic review and meta- analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM ( T1DM ) and type 2 DM ( T2DM ) . | BACKGROUND AIMS Stem cell therapy ( SCT ) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus ( T1DM ) . METHODS Our study was a prospect i ve , open-labeled , two-armed trial for 10 T1DM patients in each arm of allogenic and autologous adipose-derived insulin-secreting mesenchymal stromal cells (IS-AD-MSC)+bone marrow-derived hematopoietic stem cell ( BM-HSC ) infusion . Group 1 received autologous SCT : nine male patients and one female patient ; mean age , 20.2 years , disease duration 8.1 years ; group 2 received allogenic SCT : six male patients and four female patients , mean age , 19.7 years and disease duration , 7.9 years . Glycosylated hemoglobin ( HbA1c ) was 10.99 % ; serum ( S. ) C-peptide , 0.22 ng/mL and insulin requirement , 63.9 IU/day in group 1 ; HbA1c was 11.93 % , S.C-peptide , 0.028 ng/mL and insulin requirement , 57.55 IU/day in group 2 . SCs were infused into the portal+thymic circulation and subcutaneous tissue under non-myelo-ablative conditioning . Patients were monitored for blood sugar , S.C-peptide , glutamic acid decarboxylase antibodies and HbA1c at 3-month intervals . RESULTS Group 1 received mean SCs 103.14 mL with 2.65 ± 0.8 × 10(4 ) ISCs/kg body wt , CD34 + 0.81 % and CD45-/90+/73 + , 81.55 % . Group 2 received mean SCs 95.33 mL with 2.07 ± 0.67 × 10(4 ) ISCs/kg body wt , CD34 + 0.32 % and CD45-/90+/73 + 54.04 % . No untoward effect was observed with sustained improvement in HbA1c and S.C-peptide in both groups with a decrease in glutamic acid decarboxylase antibodies and reduction in mean insulin requirement . CONCLUSIONS SCT is a safe and viable treatment option for T1DM . Autologous IS-AD-MSC+ BM-HSC co-infusion offers better long-term control of hyperglycemia as compared with allogenic SCT CONTEXT Type 1 diabetes mellitus ( DM ) results from a cell-mediated autoimmune attack against pancreatic beta cells . Previous animal and clinical studies suggest that moderate immunosuppression in newly diagnosed type 1 DM can prevent further loss of insulin production and can reduce insulin needs . OBJECTIVE To determine the safety and metabolic effects of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation ( AHST ) in newly diagnosed type 1 DM . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve phase 1/2 study of 15 patients with type 1 DM ( aged 14 - 31 years ) diagnosed within the previous 6 weeks by clinical findings and hyperglycemia and confirmed with positive antibodies against glutamic acid decarboxylase . Enrollment was November 2003-July 2006 with observation until February 2007 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto , Ribeirão Preto , Brazil . Patients with previous diabetic ketoacidosis were excluded after the first patient with diabetic ketoacidosis failed to benefit from AHST . Hematopoietic stem cells were mobilized with cyclophosphamide ( 2.0 g/m2 ) and granulocyte colony-stimulating factor ( 10 microg/kg per day ) and then collected from peripheral blood by leukapheresis and cryopreserved . The cells were injected intravenously after conditioning with cyclophosphamide ( 200 mg/kg ) and rabbit antithymocyte globulin ( 4.5 mg/kg ) . MAIN OUTCOME MEASURES Morbidity and mortality from transplantation and temporal changes in exogenous insulin requirements ( daily dose and duration of usage ) . Secondary end points : serum levels of hemoglobin A1c , C-peptide levels during the mixed-meal tolerance test , and anti-glutamic acid decarboxylase antibody titers measured before and at different times following AHST . RESULTS During a 7- to 36-month follow-up ( mean 18.8 ) , 14 patients became insulin-free ( 1 for 35 months , 4 for at least 21 months , 7 for at least 6 months ; and 2 with late response were insulin-free for 1 and 5 months , respectively ) . Among those , 1 patient resumed insulin use 1 year after AHST . At 6 months after AHST , mean total area under the C-peptide response curve was significantly greater than the pretreatment values , and at 12 and 24 months it did not change . Anti-glutamic acid decarboxylase antibody levels decreased after 6 months and stabilized at 12 and 24 months . Serum levels of hemoglobin A(1c ) were maintained at less than 7 % in 13 of 14 patients . The only acute severe adverse effect was culture-negative bilateral pneumonia in 1 patient and late endocrine dysfunction ( hypothyroidism or hypogonadism ) in 2 others . There was no mortality . CONCLUSIONS High-dose immunosuppression and AHST were performed with acceptable toxicity in a small number of patients with newly diagnosed type 1 DM . With AHST , beta cell function was increased in all but 1 patient and induced prolonged insulin independence in the majority of the patients OBJECTIVE To determine if autologous nonmyeloablative hematopoietic stem cell transplantation ( AHSCT ) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis ( DKA ) at diagnosis . RESEARCH DESIGN AND METHODS We enrolled 28 patients with type 1 diabetes , aged 14–30 years , in a prospect i ve AHSCT phase II clinical trial . HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin . Changes in the exogenous insulin requirement were observed and serum levels of HbA1c , C-peptide , and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT . RESULTS After transplantation , complete remission ( CR ) , defined as insulin independence , was observed in 15 of 28 patients ( 53.6 % ) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months . The non-DKA patients achieved a greater CR rate than the DKA patients ( 70.6 % in non-DKA vs. 27.3 % in DKA , P = 0.051 ) . In the non-DKA group , the levels of fasting C-peptide , peak value during oral glucose tolerance test ( Cmax ) , and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up ( all P < 0.05 ) . In the DKA group , significant elevation of fasting C-peptide levels and Cmax levels was observed only at 18 and 6 months , respectively . There was no mortality . CONCLUSIONS We have performed AHSCT in 28 patients with type 1 diabetes . The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease . This prospect i ve , r and omized , single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation ( ABMSCT ) in T2DM . Twenty-one patients with triple oral antidiabetic drug failure and requiring insulin ≥0.4 IU per kg per day with HbA1c < 7.5 % were r and omly assigned to an intervention ( n = 11 ) and control group ( n = 10 ) and followed for 12 months . Patients in the intervention group received ABMSCT through a targeted approach , and after 12 weeks , a second dose of stem cells was administered through the antecubital vein after mobilization with G-CSF , while the control group underwent a sham procedure . The primary end point was a reduction in insulin requirement by ≥50 % from baseline while maintaining HbA1c < 7 % . Nine out of the 11 ( 82 % ) patients in the intervention group achieved the primary end point , whereas none of the patients in the control group did over the study period ( p = 0.002 ) . The insulin requirement decreased by 66.7 % in the intervention group from 42.0 ( 31.0 - 64.0 ) IU per day to 14.0 ( 0.0 - 30.0 ) IU per day ( p = 0.011 ) , while in controls it decreased by 32.1 % from 40.5 ( 31.8 - 44.3 ) IU per day to 27.5 ( 23.5 - 33.3 ) IU per day ( p = 0.008 ) at 12 months . The reduction in insulin requirement was significantly more in the intervention group compared to controls at both 6 ( p = 0.001 ) and 12 months ( p = 0.004 ) . There was a modest but nonsignificant increase in HbA1c ( % ) in cases from 6.9 % ( 6.4 - 7.2 % ) to 7.1 % ( 6.6 - 7.5 % ) as well as in controls from 6.9 % ( 6.2 - 7.0 % ) to 7.0 % ( 6.9 - 7.5 % ) . Ten out of 11 ( 91 % ) patients could maintain HbA1c < 7 % in the intervention group , whereas 6 out of 10 did ( 60 % ) in the control group ( p = 0.167 ) . The glucagon-stimulated C-peptide significantly increased in treated cases compared to controls ( p = 0.036 ) . The decrease in insulin requirement positively correlated with stimulated C-peptide ( r = 0.8 , p = 0.001 ) . In conclusion , ABMSCT results in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM . However , a greater number of patients with a longer duration of follow-up are required to substantiate these observations Introduction Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus ( T2DM ) . However , no data are available on the efficacy and safety of allogeneic Wharton ’s Jelly-derived mesenchymal stem cell ( WJ-MSC ) transplantation in patients with T2DM . Here we performed a non-placebo controlled prospect i ve phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM . Methods Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection ( catheterization ) . They were followed up for 12 months after transplantation . The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage , fasting blood glucose ( FBG ) , post-meal blood glucose ( PBG ) , inflammatory markers and T lymphocyte counts . Results WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin , improved C-peptide levels and beta cell function , and reduced markers of systemic inflammation and T lymphocyte counts . No major WJ-MSC transplantation-related adverse events occurred , but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment , possibly related to intrapancreatic endovascular injection . Conclusions Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM . The therapeutic mechanism may involve improvements in systemic inflammation and /or immunological regulation . Trial registration Chinese Clinical Trial Register ChiCTR-ONC-10000985 . Registered 23 September Drugs targeting β-cells have provided new options in the management of T2DM ; however , their role in β-cell regeneration remains elusive . The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells ( ABM-MSCs ) and mononuclear cells ( ABM-MNCs ) seems to offer a pragmatic approach to augment β-cell function/mass . This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies . Thirty patients of T2DM with duration of disease ≥5 years , receiving triple oral antidiabetic drugs along with insulin ( ≥0.4 IU/Kg/day ) with HbA1c ≤7.5%(≤58.0 mmol/mol ) , were r and omized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure ( n = 10 each ) . The primary endpoint was a reduction in insulin requirement by ≥50 % from baseline , while maintaining HbA1c < 7.0 % ( < 53.0 mmol/mol ) during 1-year follow-up . Six of 10 ( 60 % ) patients in both the ABM-MSC and ABM-MNC groups , but none in the control group , achieved the primary endpoint . At 12 months , there was a significant reduction in insulin requirement in ABM-MSC ( P < 0.05 ) and ABM-MNC groups ( P < 0.05 ) , but not in controls ( P = 0.447 ) . There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC ( P < 0.05 ) group , whereas a significant improvement in insulin sensitivity index ( P < 0.05 ) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group . In conclusion , both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM . Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies Type 1 diabetes mellitus ( T1DM ) is an autoimmune disorder result ed from T cell-mediated destruction of pancreatic β-cells , how to regenerate β-cells and prevent the autoimmune destruction of remnant and neogenetic β-cells is a tough problem . Immunomodulatory propertity of mesenchymal stem cell make it illuminated to overcome it . We assessed the long-term effects of the implantation of Wharton 's jelly-derived mesenchymal stem cells ( WJ-MSCs ) from the umbilical cord for Newly-onset T1DM . Twenty-nine patients with newly onset T1DM were r and omly divided into two groups , patients in group I were treated with WJ-MSCs and patients in group II were treated with normal saline based on insulin intensive therapy . Patients were followed-up after the operation at monthly intervals for the first 3 months and thereafter every 3 months for the next 21 months , the occurrence of any side effects and results of laboratory examinations were evaluated . There were no reported acute or chronic side effects in group I compared with group II , both the HbA1c and C peptide in group I patients were significantly better than either pretherapy values or group II patients during the follow-up period . These data suggested that the implantation of WJ-MSCs for the treatment of newly-onset T1DM is safe and effective . This therapy can restore the function of islet β cells in a longer time , although precise mechanisms are unknown , the implantation of WJ-MSCs is expected to be an effective strategy for treatment of type1 diabetes Background This study explored the details of the immune response after autologous hematopoietic stem cell transplantation ( AHSCT ) treatment in type 1 diabetes mellitus . Methods Peripheral blood mononuclear cells ( P BMC s ) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy . The lymphocyte proliferation , mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 ( Th1 ) , T-helper type 17 ( Th17 ) and regulatory T ( Treg ) cells in P BMC culture supernatants were assessed . Results Compared with patients receiving insulin-only treatment , the patients receiving AHSCT treatment showed better residual C-peptide secretion , lower anti-GAD titers and less exogenous insulin dosages after 12 months of follow-up . AHSCT treatment was associated with significantly reduced Th1 and Th17 cell proportions as well as decreased IFN-γ , IL-2 , IL-12p40 and IL-17A levels in the P BMC culture supernatants ( all P < 0.05 ) . Although there was no significant Treg cell expansion after AHSCT treatment , we observed increased IL-10 , TGF-β and Foxp3 mRNA expression and increased TGF-β levels . However , we found no significant changes in the T-cell sub population s after insulin treatment , except for higher IL-12p40 mRNA expression and a lower proportion of Treg cells . Conclusions AHSCT treatment was associated with decreased expansion and function of Th1 and Th17 cells , which may explain the better therapeutic effect of AHSCT compared with the traditional intensive insulin therapy . Trial registration Clinical trials.gov NCT00807651 . Registered 18 December 2008 OBJECTIVE To assess the safety , tolerability , and feasibility of adult allogeneic bone marrow – derived mesenchymal precursor cells ( MPCs ) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent . RESEARCH DESIGN AND METHODS The study was a dose-escalating r and omized placebo-controlled trial assessing one intravenous ( IV ) infusion of MPCs ( rexlemestrocel-L ; Mesoblast Inc. ) 0.3 × 106/kg ( n = 15 ) , 1.0 × 106/kg ( n = 15 ) , or 2.0 × 106/kg ( n = 15 ) or placebo ( n = 16 ) . Study duration was 12 weeks . RESULTS Subjects ( 21 women , 40 men ) with a mean ± SD baseline HbA1c 8.3 ± 1.0 % ( 67 ± 10.9 mmol/mol ) , BMI 33.5 ± 5.5 kg/m2 , and diabetes duration 10.1 ± 6.0 years were enrolled at 18 U.S. sites . No acute adverse events ( AEs ) were associated with infusion . No serious AEs , serious hypoglycemia AEs , or discontinuations due to AEs over 12 weeks were found . No subjects developed donor-specific anti-HLA antibodies or became sensitized . The safety profile was comparable among treatment groups . Compared with placebo , a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1 . The adjusted least squares mean ± SE dose-related differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from −0.1 ± 0.2 % ( −1.1 ± 2.2 mmol/mol ) to −0.4 ± 0.2 % ( 4.4 ± 2.2 mmol/mol ) at 8 weeks and from 0.0 ± 0.25 % to −0.3 ± 0.25 % ( −3.3 ± −2.7 mmol/mol ) at 12 weeks ( P < 0.05 for 2.0 × 106/kg dose at 8 weeks ) . The clinical target HbA1c < 7 % ( 53 mmol/mol ) was achieved by 33 % ( 5 of 15 ) of the subjects who received the 2.0 × 106/kg dose vs. 0 % of those who received placebo ( P < 0.05 ) . CONCLUSIONS This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes 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 AIMS The use of bone marrow mononuclear cells ( BM-MNCs ) has achieved great outcomes in clinical practice . We aim to evaluate the efficacy and safety of autologous BM-MNC infusion and hyperbaric oxygen therapy ( HOT ) in type 2 diabetes mellitus . METHODS This single-center , r and omized , open-label , controlled clinical trial with a factorial design included two phases . The patients received st and ard medical therapy in the run-in phase ; in the treatment phase , patients with glycated hemoglobin of 7.5 - 9.5 % were r and omly assigned into four groups and underwent BM-MNC infusion along with HOT ( BM-MNC+HOT group ) , BM-MNC infusion ( BM-MNC group ) , HOT ( HOT group ) and st and ard medical therapy ( control group ) , respectively . The area under the curve of C-peptide was recorded as a primary end point . Our research is registered at Clinical Trials.gov ( NCT00767260 ) . RESULTS A total of 80 patients completed the follow-up . At 12 months after treatment , the area under the curve of C-peptide ( ng/mL per 180 min ) of the BM-MNC+HOT group and the BM-MNC group were significantly improved ( 34.0 % and 43.8 % from the baseline , respectively ) . The changes were both significant compared with that in the control group , but no remarkable change was observed in the HOT group . Treatment-related adverse events were mild , including transient abdominal pain ( n = 5 ) and punctual hemorrhage ( n = 3 ) . CONCLUSIONS BM-MNC infusion for type 2 diabetes mellitus improves islet function and metabolic control , with mild adverse effects . HOT does not synergize with BM-MNC infusion Type I diabetes mellitus is a metabolic disease caused by chronic immune attack against the insulin-producing cells of the pancreas . It has recently been shown that the clinical course of this disease can be interrupted by immune ablation and PBSCT . In this report , we describe our experience with this treatment modality in a series of eight cases . Patients with newly diagnosed type I diabetes were received treatment consisting of two to three plasmaphereses , hematopoietic stem cell mobilization with CY and G-CSF , collection of at least 3 × 106 per kg of CD34 + cells , and conditioning with CY and anti-thymocyte globulin followed by stem cell infusion . All patients became independent of exogenous insulin after the transplantation . One patient resumed low-dose insulin 7 months after transplantation . Six out of eight patients were given acarbose for better glycemic control after transplantation . All patients exhibited good glycemic control : the average HbA1c concentrations were 12.3 % at diagnosis , and 5.6 and 6.2 % at 3 and 6 months after transplantation , respectively . We conclude that at least temporary independence of exogenous insulin can be achieved in type I diabetes patients following immunoablation and reconstitution of the immune system with autologous PBSCs Type 1 diabetes ( T1D ) is one of the major autoimmune diseases affecting children and young adults worldwide . To date , the different immunotherapies tested have achieved insulin independence in < 5 % of treated individuals . Recently , a novel hematopoietic stem cell (HSC)–based strategy has been tested in individuals with new-onset T1D . The aim of this study was to determine the effects of autologous nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who were enrolled in two Chinese centers and one Polish center , pooled , and followed up for 48 months . A total of 59 % of individuals with T1D achieved insulin independence within the first 6 months after receiving conditioning immunosuppression therapy ( with antithymocyte globulin and cyclophosphamide ) and a single infusion of autologous HSCs , and 32 % remained insulin independent at the last time point of their follow-up . All treated subjects showed a decrease in HbA1c levels and an increase in C-peptide levels compared with pretreatment . Despite a complete immune system recovery ( i.e. , leukocyte count ) after treatment , 52 % of treated individuals experienced adverse effects . Our study suggests the following : 1 ) that remission of T1D is possible by combining HSC transplantation and immunosuppression ; 2 ) that autologous nonmyeloablative HSC transplantation represents an effective treatment for selected individuals with T1D ; and 3 ) that safer HSC-based therapeutic options are required Mesenchymal stem cells ( MSC ) have been used in clinical trials for severe diabetes , a chronic disease with high morbidity and mortality . Bone marrow is the traditional source of human MSC , but human term placenta appears to be an alternative and more readily available source . Here , the therapeutic effect of human placenta-derived MSC ( PD-MSC ) was studied in type 2 diabetes patients with longer duration , islet cell dysfunction , high insulin doses as well as poor glycemic control in order to evaluate the safety , efficacy and feasibility of PDMSC treatment in type 2 diabetes ( T2D ) . Ten patients with T2D received three intravenous infusions of PDSC , with one month interval of infusion . The total number of PDSC for each patient was ( 1.22–1.51 ) × 106/kg , with an average of 1.35 × 106/kg . All of the patients were followed up after therapy for at least 3 months . A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU ( P<0.01 ) , and the C-peptide level was increased from 4.1 ±3.7 ng/mL to 5.6 ±3.8 ng/mL ( P<0.05 ) respectively after therapy . In 4 of 10 responders their insulin doses reduced more than 50 % after infusion . The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment ( P<0.05 ) . No fever , chills , liver damage and other side effects were reported . The renal function and cardiac function were improved after infusion . The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple , safe and effective therapeutic approach for T2D patients with islet cell dysfunction . Further large-scale , r and omized and well-controlled clinical studies will be required to substantiate these observations CONTEXT Autologous hematopoietic stem cell transplantation ( AHSCT ) has the potential to induce clinical remission in patients with newly diagnosed type 1 diabetes . OBJECTIVE The objective of the study was to examine the impact of AHSCT on lymphocytes and pancreatic β-cell function . DESIGN This was a nonr and omized , open-label prospect i ve study . PATIENTS AND INTERVENTIONS Thirteen patients with new onset of type 1 diabetes , 10 of them with diabetic ketoacidosis , were subjected to AHSCT with cryopreserved CD34(+ ) progenitor cells and followed up for 31 - 54 months . MAIN OUTCOME MEASURES The numbers of different subsets of lymphocytes and the levels of serum cytokines , islet antibodies , C-peptide , and plasma glycosylated hemoglobin were longitudinally measured . RESULTS The numbers of different subsets of lymphocytes , except for CD8(+ ) T cells , in the patients before AHSCT were significantly lower than those in controls . However , all lymphocytes gradually recovered after AHSCT , accompanied by decreased levels of serum autoantibodies , IL-1 , IL-17 , and TNF-α . After AHSCT , 11 of 13 patients required significantly reduced doses of insulin for adequate glycemic control , accompanied by reduced levels of glycosylated hemoglobin but increased C-peptide concentrations . Three patients achieved exogenous insulin independence for 7 - 54 months . The survival of remaining β-cells was associated positively with the preexisting β-cell function but negatively with preexisting autoantibodies ( P < 0.05 ) . The numbers of infused CD34(+ ) cells were positively correlated with the concentrations of serum IL-10 , IL-4 , TGF-β , and fasting C-peptide but negatively correlated with the levels of serum TNF-α and insulin doses after AHSCT ( P < 0.05 ) . CONCLUSION AHSCT modulated lymphocytes and preserved β-cell function in Chinese patients with new onset of type 1 diabetes and diabetic ketoacidosis CONTEXT In 2007 , the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation ( HSCT ) in 15 patients with type 1 diabetes mellitus ( DM ) were reported . Most patients became insulin free with normal levels of glycated hemoglobin A(1c ) ( HbA(1c ) ) during a mean 18.8-month follow-up . To investigate if this effect was due to preservation of beta-cell mass , continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients . OBJECTIVE To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve phase 1/2 study of 23 patients with type 1 DM ( aged 13 - 31 years ) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti-glutamic acid decarboxylase antibodies . Enrollment was November 2003-April 2008 , with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto , Ribeirão Preto , Brazil . Hematopoietic stem cells were mobilized via the 2007 protocol . MAIN OUTCOME MEASURES C-peptide levels measured during the mixed-meal tolerance test , before , and at different times following HSCT . Secondary end points included morbidity and mortality from transplantation , temporal changes in exogenous insulin requirements , and serum levels of HbA(1c ) . RESULTS During a 7- to 58-month follow-up ( mean , 29.8 months ; median , 30 months ) , 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free . Twelve patients maintained this status for a mean 31 months ( range , 14 - 52 months ) and 8 patients relapsed and resumed insulin use at low dose ( 0.1 - 0.3 IU/kg ) . In the continuous insulin-independent group , HbA(1c ) levels were less than 7.0 % and mean ( SE ) area under the curve ( AUC ) of C-peptide levels increased significantly from 225.0 ( 75.2 ) ng/mL per 2 hours pretransplantation to 785.4 ( 90.3 ) ng/mL per 2 hours at 24 months posttransplantation ( P < .001 ) and to 728.1 ( 144.4 ) ng/mL per 2 hours at 36 months ( P = .001 ) . In the transient insulin-independent group , mean ( SE ) AUC of C-peptide levels also increased from 148.9 ( 75.2 ) ng/mL per 2 hours pretransplantation to 546.8 ( 96.9 ) ng/mL per 2 hours at 36 months ( P = .001 ) , which was sustained at 48 months . In this group , 2 patients regained insulin independence after treatment with sitagliptin , which was associated with increase in C-peptide levels . Two patients developed bilateral nosocomial pneumonia , 3 patients developed late endocrine dysfunction , and 9 patients developed oligospermia . There was no mortality . CONCLUSION After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM , C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00315133 Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus ( T2DM ) and beta-cell regeneration using stem cell therapy may prove to be an effective modality . A total of 10 patients ( 8 men ) with T2DM for > 5 years , failure of triple oral antidiabetic drugs , currently on insulin ( > or = 0.7 U/kg/day ) at least for 1 year , and glutamic acid decarboxylase antibody negative were included . Patients on stable doses of medications for past 3 months were recruited . Primary end points were reduction in insulin requirement by > or = 50 % and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation ( SCT ) , while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline . Seven patients were responders and showed a reduction in insulin requirement by 75 % as compared to baseline . Mean duration to achieve the primary objective was 48 days . Three patients were able to discontinue insulin completely , although it was short-lived in one . Mean HbA1c reduction was 1 % and 3 of the 7 responders had HbA1c value < 7 % . A significant weight loss of 5.5 kg was noted in the responders , whereas , nonresponders gained 2.2 kg of weight . However , weight loss did not correlate with reduction in insulin requirement ( r = 0.68 , P = 0.06 ) . There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group ( P = 0.03 ) and responders ( P = 0.03 ) . HOMA-B increased significantly in the whole group ( P = 0.02 ) and responders ( P = 0.04 ) whereas , HOMA-IR did not change significantly ( P = 0.74 ) . Reduction in insulin doses correlated with stimulated C-peptide response at the baseline ( r = 0.83 , P = 0.047 ) and mononuclear cell count of infused stem cells ( r = 0.57 , P = 0.04 ) . No serious adverse effects were noted . Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM . However , further large-scale studies are needed to substantiate these observations |
474 | 32,253,560 | High IAP was not associated with a significant difference for these outcomes when compared with st and ard or low IAP .
No significant differences were found between the IAP levels regarding need for conversion to open surgery ; post-operative acute bleeding , pain at 72 h , nausea , and vomiting ; and duration of surgery .
Our study of published trials indicates that using low , as opposed to st and ard , IAP during laparoscopic cholecystectomy may reduce patients ’ post-operative pain , including shoulder pain , and length of hospital stay . | Laparoscopic cholecystectomy involves using intra-abdominal pressure ( IAP ) to facilitate adequate surgical conditions .
However , there is no consensus on optimal IAP levels to improve surgical outcomes .
Therefore , we conducted a systematic literature review ( SLR ) to examine outcomes of low , st and ard , and high IAP among adults undergoing laparoscopic cholecystectomy . | Background The incidence of shoulder pain ( SP ) following laparoscopic cholecystectomy ( LC ) varies between 21 and 80 % . A few r and omised controlled trials and meta- analysis have shown lesser SP in LC performed under low-pressure carbon dioxide pneumoperitoneum ( LPCP ) than under st and ard-pressure carbon dioxide pneumoperitoneum ( SPCP ) . However , the possible compromise in adequate exposure and effective working space during LPCP has negatively influenced its uniform adoption for LC . Material s and methods All consecutive patients undergoing elective LC for gallstone disease who met the inclusion and exclusion criteria were enroled . Fourty patients were r and omised to SPCP group ( pressure of 14 mmHg ) and 40 to LPCP group ( pressure of 9–10 mmHg ) . Primary outcome measured was incidence of SP and its severity on visual analogue scale ( VAS ) at 4 , 8 , 24 h and 7 days after LC . Secondary outcomes measured were procedural time , technical difficulty , surgeons ’ satisfaction score on exposure and working space , intra-operative changes in heart rate and blood pressure , abdominal pain and analgesic requirement . Analyses were performed using Stata software . Results There was no conversion to open surgery , bile duct injury or need to increase intra-abdominal pressure on either group . Twenty-three patients ( 57.5 % ) in SPCP group and nine patients ( 22.5 % ) in LPCP group had SP ( p = 0.001 ) . The severity of SP was significantly more in SPCP group at 8 and 24 h ( p = 0.009 and 0.005 , respectively ) . Both the groups had similar procedural time , surgeons ’ satisfaction score , intra-operative changes in heart rate and blood pressure . Conclusion The incidence and severity of SP following LC performed at LPCP are significantly less compared to that in SPCP . The safety , efficacy and surgeons ’ satisfaction appear to be comparable in both the groups . Hence , a routine practice of low-pressure carbon dioxide pneumoperitoneum may be recommended in selected group of patients undergoing laparoscopic cholecystectomy . Clinical trial registration numbe rCT RI/2016/02/006590 Background Post-laparoscopic pain syndrome is well recognized and characterized by abdominal and particularly shoulder tip pain ; it occurs frequently following laparoscopic cholecystectomy . The etiology of post-laparoscopic pain can be classified into three aspects : visceral , incision , and shoulder . The origin of shoulder pain is only partly understood , but it is commonly assumed that the cause is overstretching of the diaphragmatic muscle fibers owing to a high rate of insufflations . This study aim ed to compare the frequency and intensity of shoulder tip pain between low-pressure ( 7 mmHg ) and st and ard-pressure ( 14 mmHg ) in a prospect i ve r and omized clinical trial . Methods One hundred and forty consecutive patients undergoing elective laparoscopic cholecystectomy were r and omized prospect ively to either high- or low-pressure pneumoperitoneum and blinded by research nurses who assessed the patients during the postoperative period . The statistical analysis included sex , mean age , weight , American Society of Anesthesiologists ( ASA ) grade , operative time , complication rate , duration of surgery , conversion rate , postoperative pain by using visual analogue scale , number of analgesic injections , incidence and severity of shoulder tip pain , and postoperative hospital stay . p < 0.05 was considered indicative of significance . Results The characteristics of the patients were similar in the two groups except for the predominance of males in the st and ard-pressure group ( controls ) . The procedure was successful in 68 of 70 patients in the low-pressure group compared with in 70 patients in the st and ard group . Operative time , number of analgesic injections , visual analogue score , and length of postoperative days were similar in both groups . Incidence of shoulder tip pain was higher in the st and ard-pressure group , but not statistically significantly so ( 27.9 % versus 44.3 % ) ( p = 0.100 ) . Conclusions Low-pressure pneumoperitoneum tended to be better than st and ard-pressure pneumoperitoneum in terms of lower incidence of shoulder tip pain , but this difference did not reach statistical significance following elective laparoscopic cholecystectomy Laparoscopy using carbon dioxide insufflation induces adverse effects in both the cardiovascular and the respiratory function . The use of low pressure pneumoperitoneum has been shown to reduce adverse hemodynamic effects . However , its effect on tissue trauma and postoperative pain and recovery remains controversial . The aim of this study was to compare tissue trauma , postoperative pain , and recovery in two groups of patients undergoing laparoscopic cholecystectomy , one at insufflation pressure of 8 ( LC8 ) and the other at 15 mm Hg ( LC15 ) . Forty patients were r and omized , 20 in each group . The characteristics of the patients were similar in the two groups . The procedure was completed in all patients in the LC15 group , but in 2 patients in the LC8 group the pressure was increased to 15 mm Hg to complete the operation . There were no significant differences in postoperative pain scores , analgesic consumption , and the incidence of nausea , vomiting , and shoulder pain between the two groups . C-reactive protein concentrations and white blood cell count rose significantly after surgery , but the increase was similar in the two groups . The median duration of surgery was similar , 23 minutes ( range 15–65 ) in the LC8 group and 25 minutes ( range 15–80 ) in the LC15 group . Using our technique of laparoscopic cholecystectomy , there were no advantages to tissue damage , postoperative pain , and recovery when a low pressure pneumoperitoneum was used BACKGROUND Abdominal pain and shoulder tip pain after laparoscopic cholecystectomy are distressing for the patient . Various causes of this pain are peritoneal stretching and diaphragmatic irritation by high intra-abdominal pressure caused by pneumoperitoneum . We design ed a study to compare the post operative pain after laparoscopic cholecystectomy at low pressure ( 7 - 8 mm of Hg ) and st and ard pressure technique ( 12 - 14 mm of Hg ) . Aim : To compare the effect of low pressure and st and ard pressure pneumoperitoneum in post laparoscopic cholecystectomy pain . Further to study the safety of low pressure pneumoperitoneum in laparoscopic cholecystectomy . SETTING S AND DESIGN A prospect i ve r and omised double blind study . MATERIAL S AND METHODS A prospect i ve r and omised double blind study was done in 100 ASA grade I & II patients . They were divided into two groups -50 each . Group A patients underwent laparoscopic cholecystectomy with low pressure pneumoperitoneum ( 7 - 8 mm Hg ) while group B underwent laparoscopic cholecystectomy with st and ard pressure pneumoperitoneum ( 12 - 13 mm Hg ) . Both the groups were compared for pain intensity , analgesic requirement and complications . STATISTICAL ANALYSIS Demographic data and intraoperative complications were analysed using chi-square test . Frequency of pain , intensity of pain and analgesics consumption was compared by applying ANOVA test . RESULTS Post-operative pain score was significantly less in low pressure group as compared to st and ard pressure group . Number of patients requiring rescue analgesic doses was more in st and ard pressure group . This was statistically significant . Also total analgesic consumption was more in st and ard pressure group . There was no difference in intraoperative complications . CONCLUSION This study demonstrates the use of simple expedient of reducing the pressure of pneumoperitoneum to 8 mm results in reduction in both intensity and frequency of post-operative pain and hence early recovery and better outcome .This study also shows that low pressure technique is safe with comparable rate of intraoperative complications Postoperative shoulder‐tip pain occurs frequently following laparoscopic cholecystectomy . The aim of this r and omized clinical trial was to evaluate the efficacy of a low‐pressure carbon dioxide pneumoperitoneum during laparoscopic surgery in reducing the incidence of postoperative shoulder‐tip pain BACKGROUND Laparoscopic cholecystectomy ( LC ) has become the st and ard treatment for gall bladder disease . However , despite its low degree of invasiveness , many patients complain of postoperative pain and postoperative nausea/vomiting . This study was planned to evaluate different factors affecting the incidence and severity of postoperative shoulder-tip pain after LC . PATIENTS AND METHODS One hundred consecutive patients who were treated for gall bladder stone by LC at the Gastroenterology Surgical Center , Mansoura University , Mansoura , Egypt , during the period from October 2008 to January 2010 , were r and omized according to different pnemoperitonum pressures ( 8 , 10 , 12 , and 14 mm Hg ) . Each group comprises 25 patients . RESULTS There were 62 patients reported to have postoperative shoulder-tip pain during the first 12 hours after operation , which decreased to 9 patients on the 10th postoperative day . A significant difference was observed in the prevalence of pain at different pressures , 11 % with low pressure and increased to 20 % with high pressure . The incidence of shoulder-tip pain was significantly more in patients with a longer duration of the operation of > 45 minutes at 12 hours ( 23 [ 76.7 % ] versus 39 [ 55.7 % ] ; P = 0.04 ) , at 24 hours ( 23 [ 76.7 % ] versus 29 [ 41.4 % ] ; P = 0.009 ) , and at 3 days postoperatively ( 19 [ 63.3 % ] versus 20 [ 28.6 % ] ; P = 0.01 ) . The volume of used gases during the operation had no effect on the incidence or severity of shoulder-tip pain after LC . Also , the use of intraoperative analgesics had no effect on the incidence or severity of shoulder-tip pain after LC . CONCLUSIONS The origin of pain after LC is multifactorial . We recommend the use of the lower pressure technique during LC , and as patients with and without drains have similar incidence of postoperative shoulder pain , drains should not be used with the intention of preventing shoulder pain Abstract Background : Peritoneal insufflation to 15 mmHg diminishes venous return and reduces cardiac output . Such changes may be dangerous in patients with a poor cardiac reserve . The aim of this study was to investigate the hemodynamic effects of high ( 15 mmHg ) and low ( 7 mmHg ) intraabdominal pressure during laparoscopic cholestectomy ( LC ) Methods : Twenty patients were r and omized to either high- or low-pressure capnoperitoneum . Anesthesia was st and ardized , and the end-tidal CO2 was maintained at 4.5 kPa . Arterial blood pressure was measured invasively . Heart rate , stroke volume , and cardiac output were measured by transesophageal doppler . Results : There were 10 patients in each group . In the high-pressure group , heart rate ( HR ) and mean arterial blood pressure ( MABP ) increased during insufflation . Stroke volume ( SV ) and cardiac output were depressed by a maximum of 26 % and 28 % ( SV 0.1 > p > 0.05 , cardiac output p > 0.1 ) . In the low-pressure group , insufflation produced a rise in MABP and a peak rise in both stroke volume and cardiac output of 10 % and 28 % , respectively ( p < 0.05 ) . Conclusions : Low-pressure pneumoperitoneum is feasible for LC and minimizes the adverse hemodynamic effects of peritoneal insufflation Introduction Intraabdominal CO2 gas after laparoscopic cholecystectomy causes postoperative shoulder-tip pain . Many methods of analgesia have been used to reduce this pain , including analgesic drugs , intraperitoneal local anesthetic , intraperitoneal saline , a gas drain , heated gas , low-pressure gas , and nitrous oxide pneumoperitoneum . The aim of this study was to evaluate the efficacy of combined low-pressure CO2 pneumoperitoneum and intraperitoneal infusion of normal saline in reducing the incidence of postoperative shoulder-tip pain . Methods Altogether , 109 patients undergoing elective laparoscopic cholecystectomy were r and omized prospect ively into three groups . Patients in group A ( n = 34 ) underwent laparoscopic cholecystectomy with 14 mmHg CO2 pneumoperitoneum ; patients in group B ( n = 37 ) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum ; and those in group C ( n = 38 ) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum in addition to intraperitoneal normal saline infusion in the right hemidiaphragmatic area . Shoulder-tip pain was recorded on a verbal rating scale 2 , 6 , 12 , 24 , and 48 hours after operation . Results Twelve patients in group A ( 35.2 percent ) , six in group B ( 16.2 percent ) , and seven in group C ( 18.4 percent ) complained of shoulder-tip pain . Hence , there was a significant decrease in the frequency of shoulder-tip pain in groups B and C in relation to group A , but there was no significant difference between groups B and C. The postoperative shoulder-tip pain scores were significantly reduced in group C at 6 , 12 , and 24 hours . The number of patients who required additional analgesics was also reduced in group C. Conclusions Low-pressure CO2 pneumoperitoneum reduces the number of patients complaining of shoulder-tip pain and the intensity of the pain after laparoscopic cholecystectomy . The addition of intraperitoneal normal saline infusion to low-pressure CO2 pneumoperitoneum seems to reduce the intensity but not the frequency of shoulder-tip pain after laparoscopic cholecystectomy BACKGROUND The observation of hemodynamic and metabolic impairment related to CO2 pneumoperitoneum and postoperative mesenteric ischemia reports following laparoscopic procedures have raised concern about local and systemic effects of increase intraabdominal pressure during laparoscopic procedures . The present study aims to evaluate the metabolic and acid base responses of using high pressure versus low pressure pneumoperitonium in patients undergoing laparoscopic cholecystectomy in a prospect i ve r and omized clinical trial . PATIENTS AND METHOD 20 ASA I-II patients scheduled for elective laparoscopic cholecystectomy were r and omly allocated to one of two study groups ; high pressure pneumoperitoneum 12 - 14mmHg ( HPP , n=10 ) versus low pressure pneumoperitoneum 6 - 8mmHg ( LPP , n=10 ) undergoing laparoscopic cholecystectomy . Arterial blood gases and lactate levels were determined after induction of anesthesia ( before pneumoperitonium ) , then after 10 min , then 30 min after insufflations and at the end of surgery and 1 hour postoperatively . Nurses in recovery unit reported pain assessment starting postoperatively until 3 hours on a 10 mm VAS ( 0 - 10 ) . Statistical significant was established at P<0.05 . RESULT Bicarbonate was significantly ( P>0.0412 ) lower in high pressure group at 30 min and 60 min after insufflations . In high pressure group lactate levels increased significantly as compared to low pressure group , ( at 30 minutes after the establishment of abdominal pneumatic inflation P<0.006 and remained significantly increased ( P<0.001 ) until the end of surgery and one hour thereafter ) ( P<0.001 ) . The mean postoperative pain score during second hour ( VAS ) at HPP group was 7.4 + /- 1.17 which is significantly ( P < or = 0.006 ) higher than pain score in LPP group 5.0 + /- 1.886 . Shoulder tip pain was reported in 3 patients in the high pressure group and only one patient in the lower pressure group . CONCLUSION High-pressure pneumoperitonium causes statistically significant elevation in the arterial lactate level intraoperatively until one hour post operatively . It also causes higher pain score and shoulder tip pain Background and Purpose Intra-abdominal pressure created during laparoscopic cholecystectomy is accepted as a factor for postoperative pain . In this prospect i ve , r and omized , clinical study , the goal is to determine the effects of different intra-abdominal pressure values on visceral type pain . Material s and Methods Sixty women who underwent laparoscopic cholecystectomy were included in this study . Low-pressure ( 8 mm Hg ) , st and ard-pressure ( SP : 12 mm Hg ) , and high-pressure ( HP : 14 mm Hg ) groups were design ed for the study . The statistical analysis included mean age , weight , analgesic consumption , postoperative pain assessed by the Numeric Scale , duration of anesthesia , and operation . Results No statistically significant difference was found between the groups comparing age , weight , analgesic consumption , and Numeric Scale values . In terms of duration of anesthesia , statistically significant difference was found between the groups low-pressure and HP and SP and HP , and statistically significant difference was found regarding operative duration between the groups SP and HP . There was no difference between the others groups . Conclusions We think that intra-abdominal pressure has no effect on postoperative visceral pain , but has effect on duration of anesthesia and operation Background and Objective : With the safety of laparoscopic cholecystectomy ( LC ) having been established , the current stress is on reducing the postoperative morbidity associated with this procedure . Hence , this study was undertaken to compare the effect of low-pressure ( 8 mm Hg ) ( LPLC ) versus st and ard-pressure ( 12 mm Hg ) ( SPLC ) pneumoperitoneum on postoperative pain , respiratory and liver functions , the stress response , and the intraoperative surgeon comfort in patients undergoing LC . Material s and Methods : Patients undergoing LC ( n=43 ) were r and omized into the LPLC ( 8 mm Hg ) group ( n=22 ) and the SPLC ( 12 mm Hg ) group ( n=21 ) . Postoperative pain , changes in liver function , peak expiration flow rate , C-reactive protein level , and intraoperative surgeon comfort were assessed . Results : The postoperative pain scores ( P=0.003 , 0.000 , 0.001 , and 0.002 at 0 , 4 , 8 , and 24 h ) , total analgesic requirement ( P=0.001 ) , and the number ( total and good ) of dem and s for analgesic in the first 24 hours ( P=0.002 and 0.001 ) were lower in the LPLC group . The surgeon comfort in the LPLC group was significantly lesser ( P=0.000 ) . The liver function and peak expiration flow rate did not show any significant changes . C-reactive protein levels varied significantly only at 24 hours postoperatively ( P=0.001 ) . Conclusions : The use of low-pressure pneumoperitoneum ( 8 mm Hg ) for LC is associated with a significantly lower postoperative pain . However , the use of this low-pressure pneumoperitoneum can jeopardize the surgeon ’s comfort Background The mechanisms promoting postoperative peritoneal tumor dissemination are unclear . This study aim ed to investigate postoperative tumor dissemination over time on both tissue and molecular levels . Methods For this study , C57BL6 mice were r and omized into four groups : anesthesia alone ( control ) , carbon dioxide ( CO2 ) pneumoperitoneum at low ( 2 mmHg ) or high ( 8 mmHg ) intraperitoneal pressure ( IPP ) , and laparotomy . A mouse ovarian cancer cell line ( ID8 ) was injected intraperitoneally just before surgery . The groups were further subdivided into three groups , and a laparotomy was performed to evaluate tumor dissemination on postoperative day ( POD ) 7 , 14 , or 42 . Results The incidence of cancer cell invasion into the muscle layers of the abdominal wall was significantly higher in the laparotomy and high-IPP groups than in the low-IPP and control groups on PODs 7 and 42 . Expression levels of beta 1 integrin , cMet , urokinase-type plasminogen activator ( uPA ) , urokinase-type plasminogen activator receptor ( uPAR ) , and type-1 plasminogen activator inhibitor ( PAI-1 ) mRNA in the disseminated nodules were not significantly different among the four groups on POD 7 . However , the expression levels of all these genes in the disseminated nodules in the laparotomy group were significantly higher on POD 14 than on POD 7 . They then returned to control levels on POD 42 . There were no significant differences in the expression levels of any of these genes among the groups on POD 42 . Conclusions The current study suggests that the molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and CO2 pneumoperitoneum . Therefore , strategies targeting postoperative tumor dissemination likely will need to account for the surgical environment Abstract Background : Several studies have indicated that the carbon dioxide ( CO2 ) pneumoperitoneum during laparoscopy plays a role in the pathogenesis of port-site metastases . An experimental animal study was performed to investigate the impact of various pneumoperitoneum pressures on peritoneal tumor growth . Methods : In this study , 36 male WAG rats were r and omized into three groups ; two groups with different pneumoperitoneum pressures ( 16 mmHg and 4 mmHg ) and one group of gasless controls . After a pneumoperitoneum of 0.5 × 106 ml was established , 531 tumor cells were injected intra-abdominally and the pneumoperitoneum was maintained for 60 min . Peritoneal tumor growth was assessed on day 11 at autopsy . Results : Peritoneal tumor growth in the 16-mmHg group was significantly greater than in the 4-mmHg group ( p= 0.039 ) and the gasless group ( p= 0.004 ) . Conclusions : High-pressure CO2 pneumoperitoneum stimulates intra-abdominal tumor growth . The use of low insufflation pressures in laparoscopic cancer surgery should be considered Background The increase in intra-abdominal pressure by insufflation of carbon dioxide during laparoscopy brings certain changes in function of organ systems and also leads to postoperative pain . Degree of intra-abdominal pressure is directly related with such change . Laparoscopic cholecystectomy can be performed at low pressure pneumoperitoneum . However , available space for dissection is less than the high pressure pneumoperitoneum . Methods Twenty-six patients for elective laparoscopic cholecystectomy were studied in a prospect i ve , r and omized , patient , and surgeon blinded manner . The intra-abdominal pressure was kept either in low pressure ( 8 mm Hg ) or in high pressure ( 12 mm Hg ) . All patients underwent two dimensional echocardiography , pulmonary function test and color Doppler examination of lower limb vessels preoperatively and postoperatively . Arterial blood gas analysis and End Tidal CO2 monitored before insufflation , during surgery and after deflation . Pain score was measured by visual analog scale and surgeon 's comfort level was recorded . Postoperative analgesia requirement , complications , and hospital stay were recorded . Student t test used for the statistical analysis . Results Both groups match for the demographic parameters . Four patients required conversion to high pressure . Intraoperative pO2 level , postoperative pain , analgesic requirement , pulmonary function , and hospital stay were favoring low pressure pneumoperitoneum in a statistically significant manner . There was no difference between 2 groups for duration of surgery , intraoperative , and postoperative complications . However , the technical difficulties were grade d more ( statistically nonsignificant ) with low pressure pneumoperitoneum . Conclusions An uncomplicated gall stone disease can be treated by low pressure laparoscopic cholecystectomy with reasonable safety by an experienced surgeon . Though surgeons experience more difficulty in dissection during low pressure pneumoperitoneum , it is significantly advantageous in terms of postoperative pain , use of analgesics , preservation of pulmonary function , and hospital stay INTRODUCTION Insufflation of carbon dioxide during laparoscopic cholecystectomy leads to postoperative shoulder tip pain . The origin of shoulder pain is commonly assumed to be due to overstretching of the diaphragmatic muscle fibres owing to a high carbon dioxide pressure . AIMS To study the frequency and intensity of post operative shoulder tip pain in laparoscopic cholecystectomy and compare low and st and ard pressure pneumoperitoneum during laparoscopic cholecystectomy with respect to post operative shoulder tip pain . METHODS Patients admitted in the department of surgery for elective cholecystectomy were enrolled in the study . The patients were r and omly allocated to two groups ( group A and group B ) . In group A ( n = 50 ) , low pressure pneumoperitoneum ( 8 mm Hg ) and in group B ( n = 50 ) , st and ard pressure pneumoperitoneum ( 14 mm Hg ) was generated during laparoscopic cholecystectomy . Postoperative shoulder tip pain was assessed at 4 , 8 and 24 h after operation by the Visual Analogue Scale of Pain . RESULTS 14 patients ( 28 % ) in group B complained of post operative shoulder tip pain as compared to only 5 patients ( 10 % ) in group A. The mean intensity of post operative shoulder tip pain assessed by visual analogue scoring scale at 4 , 8 and 24 h was less in group A as compared to group B , although statistical significance was seen only at 4 h. Analgesic requirements and the mean length of post operative stay in the hospital were also less in group A as compared to group B. CONCLUSION Low pressure laparoscopic cholecystectomy ( LPLC ) significantly decreases the frequency and intensity of postoperative shoulder tip pain . LPLC decreases the dem and for postoperative analgesics , decreases postoperative hospital stay and hence improves the quality of life in the early stage of postoperative rehabilitation Aim : This study aim ed to investigate the advantages and disadvantages of LP ( 7 mmHg ) in comparison to SP ( 12 mm Hg ) pneumoperitoneum in a prospect i ve r and omized clinical trial . Material s and Methods : 148 consecutive patients qualified for laparoscopic cholecystectomy ( LC ) due to uncomplicated symptomatic gallstones were r and omized to either SPLC or LPLC . All the procedures were performed by the same experienced team of surgeons . The statistical analysis included sex , mean age , body mass index , ASA grade , operative time , complication rate , conversion rate , postoperative pain assessed by the Visual Analogue Scale of Pain ( VAS ) including the incidence of shoulder-tip pain , postoperative hospital stay , recovery time , and the quality of life ( QOL ) within 7 days following the operation . p < 0.05 was considered as indicative of significance . Results : Neither conversion to an open procedure nor major complications occurred in either group . The operative time was similar in both groups ( LP 55.7 ± 8.6 min vs SP 51.9 ± 8.3 min ) . The mean postoperative pain score was 6.18 ± 3.48 lower after LP than SPLC and the difference amounted to 22.2 % ( p < 0.005 ) . The incidence of shoulder-tip pain was 2.1 times lower after LP than SPLC ( p < 0.05 ) . QOL within 7 days following the operation was remarkably better after LPLC than after SPLC ( p < 0.01 ) . Conclusions : LP pneumoperitoneum is superior to SP pneumoperitoneum in terms of lower postoperative pain , a lower incidence of shoulder-tip pain , and a better QOL within 5 days following the operation . LP should be used for LC in cases of uncomplicated symptomatic gallstones as a recommended procedure as long as an adequate exposure is obtained with this technique Background and objectives Postoperative pain is one of the significant problems in laparoscopic surgery , especially during the first 6–12 h. This r and omized controlled trial aim ed to investigate the effect of combined preemptive etoricoxib 120 mg and low-pressure pneumoperitoneum for the management of pain after laparoscopic cholecystectomy ( LC ) . Patients and methods One hundred and twenty patients aged 18–75 with American Society of Anesthesiologists class I – II who were c and i date s for elective LC were recruited into the study . The patients were r and omly divided into two groups , by ‘ block of four ’ r and omization . The treatment group received preemptive etoricoxib 120 mg and intraabdominal pressure of 7 mmHg , and the control group received placebo and intraabdominal pressure of 14 mmHg . The postoperative pain score at rest was recorded utilizing a numeric rating scale at 1 , 2 , 6 , 10 , 14 , 18 , 22 , and 24 h. Pain on movement/ambulation ( cough ) was also recorded at 6 , 10 , 14 , 18 , 22 , and 24 h. Results There were no significant differences in the baseline characteristics of the two groups . The pain scores of the treatment versus control group of abdominal pain and incisional pain were significant on movement . Abdominal pain scores of the treatment group were decreased 0.98 when compared with the control group ( p = 0.017 ) , and incisional pain scores were also decreased 0.99 ( p = 0.001 ) . The incidences of postoperative shoulder/back pain were statistically significant : 41.8 % vs. 66.7 % in the treatment and control group , respectively ( p = 0.009 ) . The postoperative hospital stay in the treatment group and control group was : 1 day = 96.4 and 75.0 % , > 1 day = 3.6 and 25.0 % , respectively ( p = 0.001 ) . Conclusions A combination of preemptive etoricoxib and low-pressure pneumoperitoneum had significant effects in decreasing overall pain and the incidence of shoulder/back pain after LC and also shortened the hospital stay . Clinical trials registration numberTCTR20140213001 BACKGROUND Disadvantages related to CO2 pneumoperitoneum have led to development of the abdominal wall retractor ( AWR ) , a device design ed to facilitate laparoscopic surgery without conventional pneumoperitoneum ( 15 mmHg CO2 ) . We investigated the effects of the AWR on hemodynamics and gas exchange in humans . We also investigated whether the use of an AWR imposed extra technical difficulties for the surgeon . A pilot study revealed that cholecystectomy without low-pressure pneumoperitoneum was technically impossible . METHODS A prospect i ve r and omized controlled trial : Twenty patients undergoing laparoscopic cholecystectomy were r and omly allocated into group 1 : AWR with low-pressure pneumoperitoneum ( 5 mmHg ) , or group 2 : conventional pneumoperitoneum ( 15 mmHg ) . RESULTS Surgery using the AWR lasted longer , 72 + /- 16 min ( mean + /- SD ) vs 50 + /- 18 min compared with st and ard laparoscopic cholecystectomy . There were no differences between the groups with respect to hemodynamic parameters , although a small reduction of the cardiac output was observed using conventional pneumoperitoneum ( from 3.9 + /- 0.7 to 3 . 2 + /- 1.1 l/min ) and an increase during AWR ( from 4.2 + /- 0.9 to 5.2 + /- 1.5 l/min ) . Peak inspiratory pressures were significantly higher during conventional pneumoperitoneum compared to AWR . A slight decrease in pH accompanied by an increase in CO2 developed during pneumoperitoneum and during the use of the AWR . In both groups arterial PO2 decreased . CONCLUSIONS The results indicate that the view was impaired during use of the AWR and therefore its use was difficult and time-consuming . Possible advantages of this devices ' effects on hemodynamics and ventilatory parameters could not be confirmed in this study INTRODUCTION St and ard pressure pneumoperitoneum for laparoscopic cholecystectomy employs a pressure range of 12 - 14 mm Hg . An emerging trend has been the use of low pressure pneumoperitoneum in the range of 7 - 10 mm Hg in an attempt to lower the impact of pneumoperitoneum on the human physiology while providing adequate working space . Our study proposes to compare the use of low pressure pneumoperitoneum with the use of st and ard pressure pneumoperitoneum . METHODS A r and omised controlled trial consisting of 60 patients with symptomatic gallstone disease who underwent laparoscopic cholecystectomy , of which 30 patients were subjected to st and ard pressure pneumoperitoneum during the procedure and 30 patients to low pressure pneumoperitoneum . RESULTS Both groups were comparable in all aspects . The mean operating time with low pressure pneumoperitoneum was 49.07 + /- 5.72 minutes and with st and ard pressure pneumoperitoneum was 46.43 + /- 6.92 minutes . There was no statistically significant change in blood pressure , heart rate , pain at 6 hours , need for additional analgesia or shoulder tip pain with the use of lower pressure pneumoperitoneum . CONCLUSIONS Low pressure pneumoperitoneum benefits the patient in the form of lower intensity of postoperative pain but it does not positively impact intraoperative hemodynamics Inpatient low-pressure pneumoperitoneum laparoscopic cholecystectomy ( LPLC ) has been shown to have less postoperative pain ( especially shoulder-tip pain ) . No report so far has documented the use of lower-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy ( LC ) . A prospect i ve r and omized trial was conducted in Tung Wah Hospital , Day Surgery Centre from January 2004 to December 2004 . A total of 40 patients were recruited and 20 of whom were allocated to each arm . Outcome measures included operation time , treatment-related morbidity , mortality , postoperative pain ( eg , shoulder-tip pain ) , consumption of analgesics , and level of satisfaction . All patients in both groups could be discharged on the same day . Patients ' demographics and operation time were comparable in both groups . There were no treatment-related morbidity and mortality , nor was there any significant difference in postoperative pain . Less shoulder-tip pain was observed in the LPLC group though without significant difference ( 5 % vs. 20 % ; P=0.151 ) . Three patients in the LPLC group needed higher insufflation pressure ( 12 mm Hg ) because of inadequate exposure and adhesions , and the operations were successful in all of them . Otherwise , no conversion to open procedure was noted in both groups . The consumption of analgesics was minimal and a high level of satisfaction was achieved in both groups of patients . The present study demonstrated no difference in LPLC and st and ard-pressure pneumoperitoneum laparoscopic cholecystectomy in the outcomes of outpatient LC . Routine use of lower-pressure pneumoperitoneum in outpatient LC would not be recommended unless in selected straightforward cases Background The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood . The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg |
475 | 28,002,182 | Discussion : Unlike the general US population , there was no difference in smoking prevalence for female versus male PLWH ( both > 50 % ) indicating that HIV infection status was associated with a greater relative increase in smoking for women than men . | Background : Persons living with HIV/AIDS ( PLWH ) smoke at higher rates than other adults and experience HIV-related and non-HIV – related adverse smoking consequences .
This study conducted a systematic review to synthesize current knowledge about sex differences in smoking behaviors among PLWH . | INTRODUCTION Tobacco use is epidemic among persons living with HIV ( PLWH ) , and several studies have shown self-efficacy ( SE ) to be a predictor of successful cessation . This study examined sociobehavioral correlates of SE and its predictive value for successful cessation in a group of PLWH smokers . METHODS The study was conducted on combined patient data from 2 separate r and omized controlled trials of tobacco treatment for PLWH smokers . Both trials utilized the same SE scale at the same timepoints , and both had the same smoking cessation endpoint ( biochemically confirmed , 7-day , point prevalence abstinence at 3 months ) . Univariate and multivariate techniques were used to analyze the merged data set . RESULTS Baseline SE data were available for 272 subjects . The Self-Efficacy/Temptations Scale-Long Form demonstrated good internal reliability with overall and subscale Cronbach 's alpha of .77-.92 . Younger age , HIV risk other than injection drug use , recent alcohol use , and higher scores for anxiety , depression , loneliness , and nicotine dependence were all significantly correlated with lower baseline SE . Posttreatment SE was significantly predictive of successful cessation , whereas baseline SE was not . Subjects r and omized to the treatment interventions were significantly more likely to quit ( AOR = 2.99 [ 1.26 - 7.01 ] , p = .01 ) , and logistic regression suggested a possible mediating effect of posttreatment SE . CONCLUSIONS SE is tightly correlated with a number of modifiable affective and behavioral factors in PLWH smokers , and measures aim ed at increasing the SE to abstain in such individuals may enhance the effect of targeted tobacco treatment strategies OBJECTIVE To measure biopsychosocial domains related to tobacco use in persons living with HIV/AIDS ( PLWHAs ) . METHODS Cross-sectional interview study of 60 PLWHA smokers r and omly selected from an HIV clinic . RESULTS Participants averaged 14.4 cigarettes daily . Sixty-five percent were moderately or highly nicotine dependent , and most were motivated to quit . Substance use and depression were very common . Most reported that smoking helped them cope with depression , anxiety , and anger . Twenty-seven percent thought ( mistakenly ) that smoking raised their T-cell counts and /or helped fight infections . Referrals to quitlines or cessation programs were uncommon . CONCLUSIONS Smoking among PLWHAs is a challenging problem requiring targeted intervention strategies Persons living with HIV/AIDS who are current smokers are more likely to develop disease-related adverse health outcomes compared to nonsmokers with HIV/AIDS . However , the impact of smoking cessation on health outcomes such as symptom status and health-related quality of life ( HRQOL ) has not yet been assessed within this population . This study examined the effects of changes in smoking status on HIV-related symptom burden and health-related quality of life outcomes in a multiethnic , low-income population of persons living with HIV/AIDS . Patients ( n = 95 ) from a large , inner city HIV/AIDS clinic were enrolled in a smoking cessation trial providing nicotine replacement therapy , counseling , and self-help written material s. Biochemically verified smoking status , length of smoking abstinence , HIV-related symptom burden , and HRQOL were assessed approximately 3-months posttrial enrollment . A series of multiple linear regression models was performed to assess the associations between the smoking status variables and the health outcomes at follow-up while controlling for baseline levels . Length of smoking abstinence was significantly associated ( p = 0.02 ) with HIV-related symptom burden . Specifically , increasing number of consecutive days of smoking abstinence during the 3-month follow-up period was associated with lower levels of HIV-related symptom burden at the time of follow-up . However , 24-hour smoking prevalence was not significantly ( p > 0.05 ) associated with changes in either HIV-related symptom burden or HRQOL . These findings suggest that smoking cessation can significantly improve symptom burden for individuals living with HIV/AIDS . Moreover , these benefits are observable as early as 3 months after quitting and are positively correlated with the length of abstinence Objective : To evaluate the feasibility and preliminary efficacy of a Web-based tobacco treatment for persons living with HIV ( PLWH ) . Design : Prospect i ve , r and omized controlled trial . Setting : HIV-care center in the Bronx , New York . Subjects : Eligibility criteria included HIV infection , current tobacco usage , interest in quitting , and access to a computer with internet . One hundred thirty-eight subjects enrolled , and 134 completed the study . Intervention : Positively Smoke Free on the Web ( PSFW ) , an 8-session , 7-week targeted tobacco treatment program for PLWH , was compared with st and ard care ( brief advice to quit and self-help brochure ) . All subjects were offered nicotine patches . Main Outcome Measures : The main feasibility outcomes were number of sessions logged into , number of Web pages visited , number of interactive clicks , and total time logged in . The main efficacy outcome was biochemically verified , 7-day point prevalence abstinence 3 months after intervention . Results : PSFW subjects logged into a mean of 5.5 of 8 sessions and 26.2 of 41 pages . They executed a mean of 10 interactive clicks during a mean total of 59.8 minutes logged in . Most required reminder phone calls to complete the sessions . Educational level , anxiety score , and home access of the Web site were associated with Web site usage . Ten percent of the PSFW group vs. 4.3 % of controls achieved the abstinence end point . Among those who completed all 8 sessions , 17.9 % were abstinent , and among women completers , 30.8 % were abstinent . Conclusions : Web-based treatment is a feasible strategy for PLWH smokers , and preliminary findings suggest therapeutic efficacy Background : More than half of the persons living with human immunodeficiency virus ( HIV ; PLWH ) in the US smoke cigarettes , and tobacco use is responsible for considerable morbidity and mortality in this group . Little is known about the efficacy of tobacco treatment strategies in PLWH . Design : R and omized controlled trial comparing Positively Smoke Free ( PSF ) , an intensive group-therapy intervention targeting HIV-infected smokers , to st and ard care . Methods : A cohort of 145 PLWH smokers , recruited from an HIV-care center in the Bronx , New York , were r and omized 1:1 into the PSF program or st and ard care . All were offered a 3-month supply of nicotine replacement therapy . PSF is an 8-session program tailored to address the needs and concerns of HIV-infected smokers . The sessions were cofacilitated by a graduate student and an HIV-infected peer . The primary outcome was biochemically confirmed , 7-day point-prevalence abstinence at 3 months . Results : In the intention-to-treat analysis , PSF condition subjects had nearly double the quit rate of controls ( 19.2 % vs. 9.7 % , P = 0.11 ) . In the complete case , as-treated analysis , assignment to PSF was associated with increased odds of quitting ( odds ratioadj 3.55 , 95 % confidence interval 1.04 to 12.0 ) . Latino ethnicity and lower loneliness score were predictive of abstinence . The subjects in the PSF condition exhibited significant decreases in daily cigarette consumption and significant increases in self-efficacy and in motivation to quit . Attendance of ≥7 sessions was associated with higher quit rates . Conclusions : These findings suggest a positive effect of PSF on cessation rates in PLWH smokers . Loneliness and self-efficacy are influential factors in the smoking behaviors of PLWH Smoking is highly prevalent among HIV+ individuals and studies indicate that it may be associated with poor ART adherence , though the relationship is poorly understood . In addition little is known about interest in quitting among HIV+ smokers who are having adherence difficulties . We examined smoking and ART adherence among 203 HIV+ individuals enrolled in a r and omized trial of interventions to increase ART adherence . Prior analyses indicated there were no overall treatment group effects . Smoking status and motivation to quit was assessed at baseline and ART adherence was assessed at week 12 , 24 , 36 , and 48 . Longitudinal generalized estimating equation analysis that controlled for treatment group revealed that smoking status was not significantly related to adherence over time . Motivation to quit was high with 58 % intending to quit in the next 6 months and 25 % intending to quit in the next 30 days . Findings suggest that smoking is not associated with adherence among those with adherence difficulties . However it does not diminish importance of addressing both behaviors especially given HIV+ smokers substantial interest in changing smoking behavior . ResumenFumar es altamente prevalente entre las personas VIH-positivas y investigaciones indican que puede ser asociado con la baja adherencia a los medicamentos antiretrovirales aunque la relación no es muy entendible . Además se sabe poco sobre el interés en dejar de fumar entre los fumadores VIH-positivos que están teniendo dificultades de adherencia . Examinamos la relación entre el fumar y adherencia a los medicamentos antiretrovirales entre 203 personas VIH-positivas reclutadas a una investigación aleatoria de intervenciones para aumentar la adherencia antirretroviral . Los análisis previos indicaban que no había efectos globales del grupo de tratamiento . El consumo de tabaco y la motivación para dejar de fumar se evaluó al inicio de la investigación y la adherencia antirretroviral se evaluó en la semana 12 , 24 , 36 , y 48 . Análisis de la ecuación de estimación generalizada longitudinal control and o por el efecto del grupo de tratamiento mostro que el consumo de tabaco no se relacionó significativamente con la adherencia con el tiempo . La motivación para dejar de fumar fue alta con el 58 % de personas con intención de dejar de fumar en los próximos 6 meses y el 25 % con la intención de dejar de fumar en los próximos 30 días . Los result ados sugieren que el fumar no está asociado con la adherencia de medicamentos antiretrovirales entre las personas con dificultades de adherencia . Sin embargo , no disminuye la importancia de abordar ambas conductas especialmente dado el interés sustancial de cambiar el consumo de tabaco entre fumadores VIH-positivos Unhealthy substance-use behaviors , including a heavy alcohol intake , illicit drug use , and cigarette smoking , are engaged in by many HIV-positive individuals , often as a way to manage their disease-related symptoms . This study , based on data from a larger r and omized controlled trial of an HIV/AIDS symptom management manual , examines the prevalence and characteristics of unhealthy behaviors in relation to HIV/AIDS symptoms . The mean age of the sample ( n = 775 ) was 42.8 years and 38.5 % of the sample was female . The mean number of years living with HIV was 9.1 years . The specific self-reported unhealthy substance-use behaviors were the use of marijuana , cigarettes , a large amount of alcohol , and illicit drugs . A subset of individuals who identified high levels of specific symptoms also reported significantly higher substance-use behaviors , including amphetamine and injection drug use , heavy alcohol use , cigarette smoking , and marijuana use . The implication s for clinical practice include the assessment of self-care behaviors , screening for substance abuse , and education of persons regarding the self-management of HIV Background : Asymptomatic ischaemic heart disease ( IHD ) in HIV-infected patients has not been studied . Methods : Resting , 12-lead electrocardiograms ( ECG ) were evaluated for asymptomatic IHD ( Q-wave and /or ST segment depression ) at baseline from HIV-infected participants with no known IHD enrolling in the SMART study . The ECG recordings were st and ardized and central ly analysed . Factors associated with asymptomatic IHD were identified by logistic regression , sequentially adjusted for demographics , clinical history , metabolic risk factors and type and duration of antiretroviral therapy ( ART ) . Results : Of 4831 participants with an evaluable , baseline ECG and no prior IHD , mean age was 44 years ( SD , 9.3 ) ; 28.4 % were female ; 6.6 % had diabetes ; 16.5 % were receiving antihypertensive therapy ; and 95.4 % were ART experienced . ECG evidence of IHD was detected in 526 ( 10.9 % ) [ Q-wave in 283 ( 5.9 % ) , ST segment depression in 264 ( 5.5 % ) ] ; 16.7 % in those 60 years or older . Variables independently associated with these abnormalities were older age [ age ≥ 60 versus < 40 years : odds ratio ( OR ) , 2.2 ; 95 % confidence interval ( CI ) , 1.5–3.2 ; P < 0.001 ] , current antihypertensive therapy ( OR , 1.5 ; 95 % CI , 1.1–1.9 ; P = 0.003 ) and recruitment in Europe ( OR , 1.4 ; 95 % CI , 1.1–1.7 ; P = 0.004 ) or Asia ( OR , 1.6 ; 95 % CI , 1.0–2.6 ; P = 0.05 ) , both compared with North America . Diabetes was borderline significant ( OR , 1.4 ; 95 % CI , 1.0–2.0 ; P = 0.06 ) . Conclusions : ECG evidence of asymptomatic IHD was common in this large cohort of HIV-infected adults and more common than a history of symptomatic IHD . Traditional factors were the predominant determinants of risk . No clear association between ART type or duration and asymptomatic IHD was noted The aim of the study was to assess whether prospect i ve follow‐up data within the Swiss HIV Cohort Study can be used to predict patients who stop smoking ; or among smokers who stop , those who start smoking again INTRODUCTION Smoking is the leading cause of preventable death in the world . The prevalence of smoking is higher in people infected with HIV than in the general population . Although it is biologically plausible that smoking increases the morbidity and mortality of people living with HIV/AIDS , few studies in developing countries have analyzed the determinants and consequences of smoking in HIV infected people . OBJECTIVE To estimate the prevalence of smoking and identify the socioeconomic factors associated with smoking and smoking cessation in patients with HIV by sex . METHODS A cross-sectional study was conducted with baseline data , obtained from an ongoing prospect i ve cohort study of patients with HIV attending two referral centers in Recife , Northeast Region of Brazil , between July 2007 and October 2009 . RESULTS The prevalence of current smoking was 28.9 % . For both sexes , smoking was independently associated with heavy alcohol drinking and marijuana use . Among women , smoking was associated with living alone , not being married and illiteracy ; and among men , being 40 years or older , low income and using crack . Compared with ex-smokers , current smokers were younger and more likely to be unmarried , heavy drinkers and marijuana users . CONCLUSIONS It is important to incorporate smoking cessation interventions for the treatment of heavy alcohol drinkers and marijuana users with HIV/AIDS , which may increase life expectancy and quality of life , as smoking is related to risk of death , relapse of tuberculosis , and non communicable diseases BACKGROUND Health promotion efforts encourage smokers to quit and to use effective cessation treatments . R and omized controlled trials demonstrate that medications and behavioral treatments improve cessation rates , but retrospective surveys have been inconsistent . This study assessed frequency of quit attempts , use of treatments for cessation , and abstinence rates among treatment users and non-users . METHODS Data were analyzed from the 2003 Tobacco Use Special Cessation Supplement to the Current Population Survey . Participants included 29,537 U.S. smokers aged > or = 18 years who smoked daily 12 months before the survey . Outcome measures included past-year quit attempts ; use of behavioral , pharmacologic , and alternative treatments ; receipt of social support ; and abstinence for > or = 4 weeks at time of survey . RESULTS Approximately 43.5 % of smokers reported a quit attempt in the preceding year : 64.2 % of attempters used no cessation treatments ; 8.8 % used behavioral treatment ; 32.2 % used medication ; and 14.1 % used more than one treatment . Social support was reported to have been received by 24.1 % . More nicotine-dependent smokers were more likely to use medications ( OR=3.58 ; 95 % CI=3.04 - 4.20 ) . At the time of the survey , 19.3 % of attempters were abstinent > or = 4 weeks . Smokers who sought treatment were less likely to be abstinent ( OR=0.75 ; 95 % CI=0.67 - 0.84 ) , and those who sought multiple treatments were even less likely to be abstinent . CONCLUSIONS Many U.S. smokers make quit attempts , but most do not use behavioral or pharmacologic treatments . More nicotine-dependent smokers were more likely to seek treatment . Smokers who sought treatment were less likely to report abstinence , probably due to biased self- selection and recall . Retrospective survey data are not well-suited to assess the effectiveness of treatment Gender differences in tobacco withdrawal are of considerable clinical importance , but research findings on this topic have been mixed . Method ological variation in sample s sizes , experimental design , and measures across studies may explain the inconsistent results . The current study examined whether male ( n = 101 ) and female ( n = 102 ) smokers ( > or = 15 cigarettes/day ) differed in abstinence-induced changes on a battery of self-report measures ( withdrawal , affect , craving ) , cognitive performance tasks ( attention , psychomotor performance ) , and physiological responses ( heart rate , blood pressure , brain electroencephalogram ) . Participants attended 2 counterbalanced laboratory sessions , 1 following 12 hr of abstinence and the other following ad libitum smoking . Results showed that women reported greater abstinence-induced increases in negative affect , withdrawal-related distress , and urge to smoke to relieve withdrawal distress . In contrast , both genders reported similar abstinence-induced changes in positive affect and urge to smoke for pleasure . Men and women exhibited generally similar abstinence-induced changes in physiological and cognitive performance measures . In addition , gender did not moderate the association between withdrawal symptoms and baseline measures of smoking behavior and dependence . Abstinence-induced changes in withdrawal distress mediated the effect of gender on latency until the 1st cigarette of the day at trend levels ( p < .10 ) . These findings suggest that there are qualitative gender differences in the acute tobacco withdrawal syndrome that may underlie gender-specific smoking patterns High prevalence of tobacco use and low success in quitting remain significant problems for reducing disease burden among HIV-infected persons . This study ’s purpose was to examine participant responsiveness and tobacco dependence treatment adherence and their influences on tobacco abstinence among HIV-infected patients . This non-r and omized study included HIV-infected smokers 18 years of age or older , who smoked at least 5 cigarettes per day , and had an interest in quitting smoking in the next 30 days . HIV-infected smokers ( n = 247 ) received a 12-week tobacco dependence treatment intervention that included pharmacotherapy and telephone counseling . Younger age and non-White race were associated with lower adherence to pharmacotherapy . Younger age , non-White race , and increased monthly binge drinking were associated with lower adherence to telephone counseling . High participant responsiveness was associated with adherence to pharmacotherapy , counseling , and abstinence . Development and testing of interventions to improve adherence to evidence -based tobacco dependence treatment is warranted . ResumenLa alta prevalencia del uso de tabaco y el bajo éxito en parar su uso es un problema importante a considerar en la reducción del impacto de la enfermedad entre las personas infectadas por el VIH . Existen directivas de práctica clínica para el tratamiento efectivo de la dependencia al tabaco ; pero adherencia de los pacientes a las recomendaciones es crítico para su buen éxito . El propósito de este estudio fue examinar el grado de aceptacion al estudio , la adherencia de tratamiento de dependencia al tabaco y sus influencias sobre la abstinencia del tabaco y permanencia en pacientes infectados por el VIH . Este estudio no r and omizado incluyo fumadores infectados con HIV , de 18 años o mas , quienes fumaban por lo menos 5 cigarrillos por dia y habian manifestado el deseo de cesar de fumar en los siguientes 30 días . Fumadores infectados con VIH ( n = 247 ) recibieron una intervención de tratamiento de abstinencia por 12 semanas , incluyendo farmacoterapia y asesoramiento telefónico . Edad menor y raza no blanca se asociaron con menor adherencia al tratamiento farmacológico . Edad menor , raza no blanca , y alto número de borracheras mensualmente se asociaron con menor adherencia a consejos telefónicos . Adherencia al tratamiento de la dependencia al tabaco result ó en mayores tasas de abstinencia confirmadas bioquímicamente a los 3 meses . Pruebas muestran que intervenciones específicas para los pacientes infectados por el VIH que mejoran la adherencia al tratamiento de la dependencia del tabaco son justificables Introduction . HIV infected persons have high prevalence of smoking and tobacco-associated health risks . Few studies describe smoking cessation programs targeting this population . The Infectious Disease Practice ( IDP ) in Newark , New Jersey , initiated a smoking cessation program ( SCP ) for HIV infected smokers . We report participation , abstinence rates , and predictors of abstinence . Methods . This is a prospect i ve cohort study , comparing participants to non-SCP smokers , during April 1 , 2011 , to October 31 , 2012 . Intervention included one individualized counseling session with an offer of pharmacotherapy . Univariate and multivariate analyses were performed with self-reported seven-day point prevalence abstinence at six months as primary outcome measure . Results . Among 1545 IDP patients , 774 ( 51 % ) were current smokers of whom 123 ( 16 % ) participated in the SCP . Mean six-month abstinence rate amongst SCP participants was 16 % . A history of cocaine or heroin use was predictive of continued smoking ( odds ratio [ OR ] adjusted 0.20 , 95 % confidence interval [ CI ] 0.07–0.55 ) while smokers in the preparation stage of change were more likely abstinent at six months ( OR adjusted 8.26 , 95 % CI 1.02–66.67 ) . Conclusions . A low-intensity smoking cessation intervention in an HIV treatment setting is effective in a minority of participants . Further research is needed to better address barriers to smoking cessation such as substance use Gender differences in smoking quit rates are frequently reported and are the subject of much speculation . This study examined the generalizability of gender differences in abstinence across study sites , treatments , and time of relapse , as well as potential mediators and moderators of gender effects . Participants were smokers who participated in 3 r and omized clinical trials of the nicotine patch ( N = 632 ) . Men had higher cessation rates than women at all follow-ups . The impact of gender on abstinence was unaffected by controlling for study site , treatment , or time of relapse . There was little evidence for mediation or moderation of this relation by any of a host of predictor variables . The magnitude and consistency of the gender differential , coupled with an inability to account for it , highlights a compelling need for additional research specifically aim ed at elucidating the relation between gender and abstinence Editors ' Notes Context Smoking is associated with increased illness and death in adults with HIV . Contribution In an analysis that included both a cohort and a cross-sectional study , adults with HIV were found to smoke more and were less likely to quit smoking than the general U.S. population . Modifiable risk factors independently associated with higher smoking prevalence among persons with HIV included homelessness , incarceration , substance abuse , binge drinking , depression , and not achieving HIV viral suppression . Implication Efforts to increase smoking cessation should be a routine component of HIV care programs . Cigarette smoking is a leading cause of illness and death in the United States , accounting for 480000 adult deaths annually ( 1 ) . Moreover , the financial burden of smoking in direct medical expenses and lost productivity in the United States is high ; estimated costs are $ 289 to $ 332 billion annually ( 1 ) . For adults with HIV , cigarette smoking increases both HIV-related and nonHIV-related illness and death . Smoking-associated cancer ( such as cancer of the lung , head and neck , cervix , and anus ) has occurred at higher rates among adults with HIV than those in the general population ( 24 ) . Respiratory complications of HIV infection , including chronic obstructive pulmonary disease ( 5 ) , cryptococcal and bacterial pneumonia ( 6 , 7 ) , and pulmonary tuberculosis ( 810 ) , have been associated with smoking . Cigarette smoking is also related to cardiovascular disease ( 11 ) , a leading source of illness and death among persons with and without HIV in the United States . A recent study in Denmark found that the life-years lost among persons with HIV who smoked exceeded the estimated total losses attributed to each condition alone , suggesting that HIV infection and smoking act synergistically to increase mortality rates ( 12 ) . Despite the preventable effect of smoking on the health of persons with HIV , prevalence among a representative sample of adults with HIV in the United States has not been well-characterized . Observational studies from selected sample s of persons with HIV have suggested that smoking prevalence ranges from 40 % to 70 % ( 2 , 11 , 1317 ) . However , observations from these studies have limited generalizability due to small sample size ( 13 , 17 ) , limited demography ( 2 ) , or limited geography ( 15 ) . We report cigarette smoking prevalence estimates from a nationally representative , geographically diverse sample of U.S. adults with HIV who received medical care to address the limitations in previous studies . We also assessed factors associated with cigarette smoking among adults with HIV , compared the prevalence of cigarette smoking among adults with HIV with the prevalence of cigarette smoking in the U.S. general adult population , and compared lifetime smoking cessation , as measured by the quit ratio , between adults with HIV and the general adult population . Methods Data Sources and Study Design We used data from the Medical Monitoring Project ( MMP ) and the National Health Interview Survey ( NHIS ) to estimate the prevalence of cigarette smoking among adults with HIV and adults in the general U.S. population . The MMP is a supplemental HIV surveillance system with a multistage probability design from which estimates of behavioral and clinical characteristics of adults with HIV who received HIV medical care in the United States are derived ( 1820 ) . For the 2009 data collection cycle , data were collected between June 2009 and May 2010 using face-to-face interviews and medical record abstract ions . Of 603 facilities within the states or territories sample d to participate in the MMP , 461 participated ( facility response rate , 76 % ) . Of 9338 sample d persons , data were available for 4217 who had a completed interview linked with medical record abstract ion ( adjusted patient-level response rate , 51 % ) . Data were weighted based on known probabilities of selection in each state or territory , by facility , and for patients in selected facilities . Data were also weighted to adjust for nonresponse using predictors of patient-level response ( that is , facility size , race or ethnicity , time since HIV diagnosis , and age group ) . The Centers for Disease Control and Prevention 's ( CDC ) National Center for HIV/AIDS , Viral Hepatitis , STD , and TB Prevention has determined the MMP to be a non research public health surveillance activity used to guide disease control programs and policy ( 21 ) ; therefore , it was not review ed by a federal institutional review board . Participating states or territories and facilities obtained local institutional review board approval to conduct the MMP if required locally . Informed consent was obtained from all interviewed participants . The NHIS is a cross-sectional household interview survey with a multistage probability design that uses year-round continuous sampling and interviewing of a representative sample of households and noninstitutional group quarters ( such as college dormitories ) ( 22 ) . The 2009 NHIS adult core question naire collected national health information on illness and disability through in-person interviews with a r and om probability sample of 27731 noninstitutionalized civilian adults aged 18 years or older ; the overall response rate was 65.4 % . The NHIS data were weighted to account for the sample design ; account for the differential probability of selection and nonresponse ; and adjust for the population totals of noninstitutionalized U.S. civilians according to age , sex , and race or ethnicity ( 23 ) . Measures Smoking Status The primary outcome variable was current smoking status , defined based on respondents ' answers to the following questions : Have you smoked at least 100 cigarettes in your entire life ? ( MMP and NHIS ) ; Do you now smoke cigarettes every day , some days , or not at all ? ( NHIS only ) ; and How often do you smoke cigarettes now ? ( MMP only ) . The response categories for the latter question were daily , weekly , monthly , less than monthly , and never . Current cigarette smokers were defined as persons who reported that they had smoked 100 cigarettes or more during their lifetime and currently smoked every day or some days . Never-smokers were defined as persons who reported that they had not smoked at least 100 cigarettes in their entire life , and former smokers were defined as those who reported smoking at least 100 cigarettes during their lifetime but were not currently smoking . The quit ratio , a measure of successful smoking cessation at the population level , was defined as the ratio of former smokers to ever-smokers ( that is , the sum of current smokers and former smokers ) ( 24 ) . Demographic , Social , and Behavioral Variables Sociodemographic variables collected for the MMP analyses included age group , sex , race or ethnicity , sexual transmission risk , education , time since HIV diagnosis ( in years ) , and poverty level ( 25 ) . The following social and behavioral variables were reported by respondents based on the 12 months before their interviews : annual income , incarceration , homelessness , health insurance , depression ( 26 , 27 ) , and drug use ( both injection and noninjection ) for nonmedical purpose s. Binge drinking in the 30 days before the interview was defined as 5 or more alcoholic drinks per day for men and 4 or more drinks per day for women ( 28 ) . The number and percentage of participants meeting current poverty guidelines for the MMP were determined using the U.S. Department of Health and Human Services ( 25 ) poverty guidelines and poverty thresholds published by the U.S. Census Bureau for the NHIS in 2009 . Clinical Care Indicators Clinical MMP variables were abstract ed from participants ' medical records for the year before the interview and included geometric mean CD4 + T-lymphocyte count ( 0 to 0.199109 cells/L , 0.200 to 0.349109 cells/L , 0.350 to 0.499109 cells/L , or 0.500109 cells/L ) , plasma HIV RNA viral load ( suppression was defined as most recent viral load documented as undetectable , or 200 copies/mL ) , documented prescription of antiretroviral therapy , and disease stage per CDC criteria ( stage 1 , no AIDS and nadir CD4 + count 0.500109 cells/L [ or 29 % ] ; stage 2 , no AIDS and nadir CD4 + count between 0.200 and 0.499109 cells/L [ or 14 % to < 29 % ] ; or stage 3 , AIDS or nadir CD4 + count between 0 and 0.199109 cells/L [ or < 14 % ] ) ( 29 ) . Statistical Analysis Prevalence of and Factors Associated With Current Smoking Among Adults With HIV To identify factors associated with current smoking , we used the modified RaoScott chi-square test to measure the bivariate association between each characteristic and current smoking ( 30 ) . All characteristics that were significant at a P value less than 0.10 were included in the final multivariate logistic model , including age , sex , race or ethnicity , education level , poverty level , homelessness , incarceration , noninjection drug use , binge alcohol use , depression , geometric mean CD4 + count , and viral suppression . For all variables in the model , we computed model-adjusted prevalence differences ( shown as percentage points ) with 95 % CIs among all levels of each characteristic associated with current smoking among adults with HIV using a multivariate logistic regression model with predicted marginal means ( 31 , 32 ) . All analyses were performed using SAS , version 9.3 ( SAS Institute ) , and SAS-callable SUDAAN , version 10.0.1 ( RTI International ) , and accounted for clustering , unequal selection probabilities , and nonresponse . Comparisons Between Adults With HIV and the U.S. General Adult Population Weighted estimates , percentages , and CIs were determined for current smokers , nonsmokers , and former smokers among adults with HIV ( MMP ) and the U.S. general adult population ( NHIS ) , stratified by age group , sex , race or ethnicity , education , and poverty level . We did multivariate analyses and tested the association between current smoking and selected characteristics for both population s. Adjusted prevalence estimates ( predicted marginal percentages ) and prevalence ratios were calculated INTRODUCTION Poly-tobacco use is defined as cigarette and other tobacco consumption with either product used daily or nondaily . While concurrent use of different types of tobacco has been documented within the general population , less is known about poly-tobacco use among HIV-positive smokers and its impact on smoking cessation efforts . OBJECTIVE To characterize the profile of poly-tobacco users ( PTU ) in a sample of HIV-positive smokers participating in a cessation program . METHODS The study sample consisted of 474 HIV-positive smokers enrolled in a 2-group r and omized controlled trial of cigarette smoking cessation comparing a cell phone-based intervention to usual care . Prevalence was determined , and risk factors for poly-tobacco use were evaluated using logistic regression . RESULTS In this cohort of HIV-positive cigarette smokers , 21.6 % of participants were PTU , with cigars ( 73.4 % ) the most common tobacco product consumed . Among PTU , 73.5 % used other form(s ) of tobacco some days , and 26.5 % use them every day . Perceived discrimination and unemployment were significantly associated with poly-tobacco use after adjusting for other demographic , behavioral , and psychosocial factors . Analysis showed that participants in the cell phone group ( vs. usual care ) were more likely to report 24-hr abstinence , both among monocigarette users ( 16.6 % vs. 6.3 % , p < .001 ) and PTU ( 18.5 % vs. 0 % , p < .001 ) . CONCLUSION Poly-tobacco use prevalence among adult HIV-positive smokers was considerably higher than in the general population . Special attention must be placed on concurrent use of cigarettes and cigars among HIV-positive smokers . Because PTU are a unique population less likely to succeed in brief smoking cessation interventions , effective cessation programs are needed INTRODUCTION Low rates of adherence to smoking cessation pharmacotherapy may limit the effectiveness of treatment . However , few studies have examined adherence in smoking cessation trials thus , there is a limited underst and ing of factors that influence adherence behaviors . This brief report analyzes correlates of adherence to varenicline among people living with HIV/AIDS . METHODS Study participants were recruited from three HIV care centers in New York City and enrolled in a three-arm r and omized controlled pilot study in which all subjects received varenicline . At the 1-month study visit , there were no significant differences in adherence by study condition , therefore we combined treatment arms to examine correlates of adherence ( n = 127 ) . We used pill counts to assess varenicline adherence , defined as taking at least 80 % of the prescribed dose . We conducted a multivariate path analysis to assess factors proposed by the information-motivation-behavioral skills model to predict adherence . RESULTS Only 56 % of smokers were at least 80 % adherent to varenicline at 1 month . Adherence-related information , self-efficacy , a college degree , and non-Hispanic white race/ethnicity were associated with increased varenicline adherence . In path analysis , information and motivation were associated with increased adherence self-efficacy , and adherence self-efficacy was associated with increased adherence , but with marginal significance . These associations with adherence were no longer significant after controlling for race/ethnicity and education . CONCLUSIONS Further exploration of the role of a modifiable correlates of adherence , such as adherence-related information , motivation and self-efficacy is warranted . Interventions are needed that can address disparities in these and other psychosocial factors that may mediate poor medication adherence Five parameters of postcessation smoking withdrawal variability derived from clinical data ( T. M. Piasecki , D. E. Jorenby , S. S. Smith , M. C. Fiore , & T. B. Baker , 2003a , 2003b ) were predicted from baseline measures and pharmacotherapy assignment . Smokers who were more dependent , older , and high in negative affect reported more severe withdrawal . Women , heavier smokers , and those with a history of depression reported more variable symptoms . Smokers treated with nicotine patch , bupropion , or both reported less severe withdrawal than did those given placebo , but medication did not affect the slope of symptoms over time , day-to-day variability of symptoms , or the size of acute changes in symptoms associated with lapses to smoking . Prior research has shown that these symptom facets predict later relapse : thus , current pharmacotherapies may aid cessation by diminishing withdrawal severity , but they do not affect all clinical ly important aspects of withdrawal ABSTRACT Prevention and cessation of Tobacco use among persons living with HIV/AIDS ( PLWHA ) represents a significant challenge for HIV/AIDS patient care in China and across the globe . Awareness of HIV-positive status may alter the likelihood for PLWHA smokers to change their smoking habit . In this study , we tested the risk enhancement and risk reduction hypotheses by assessing changes in cigarette smoking behavior among PLWHA after they received the positive results of their HIV tests . Cross-sectional survey data collected from a r and om sample of 2973 PLWHA in care in Guangxi , China were analyzed . Changes in cigarette smoking after receiving the HIV-positive test results , as well as the current levels of cigarette smoking were measured . Among the total participants , 1529 ( 51.7 % ) were self-identified as cigarette smokers , of whom 436 ( 28.9 % ) reduced smoking and 286 ( 19.0 % ) quit after receiving their HIV-positive test results . Among the quitters , 210 ( 73.9 % ) remained abstinent for a median duration of two years . There were also 124 ( 8.2 % ) who increased cigarette smoking . Older age , female gender , more education , and receiving antiretroviral therapy were associated with quitting . In conclusion , our study findings support the risk reduction and risk enhancement hypotheses . A large proportion of smoking PLWHA reduced or quit smoking , while a small proportion increased smoking . Findings of this study suggest that the timing when a person receives his or her HIV-positive test result may be an ideal opportunity for care providers to deliver tobacco cessation interventions . Longitudinal studies are indicated to verify the findings of this study and to support smoking cessation intervention among PLWHA in the future BACKGROUND Antiretroviral therapy ( ART ) is a risk factor for cardiovascular disease ( CVD ) and smoking the most important modifiable cardiovascular risk factor . METHODS We prospect ively evaluated a smoking cessation programme ( SCP ) in HIV-infected individuals ( intervention : counselling and nicotine replacement therapy ) . Primary endpoint was the smoking cessation rate at 12 months ; secondary endpoints were CVD morbidity and mortality . Controls were a not r and omized control group of smokers not participating in the SCP . RESULTS Four-hundred and seventeen of 680 ( 61 % ) patients were smokers , and 34 of these participated in the SCP . Of these 34 individuals , 82 % were male , the median age was 43 years , prior AIDS was recorded in 29 % , and depressive disorder was recorded in 18/% . Twenty-five ( 74 % ) patients were receiving ART . Additional risk factors were dyslipidaemia ( 68 % ) , a prior cardiovascular event ( 24 % ) , hypertension ( 1 5 % ) , and a family history of CVD in 2/34 ( 6 % ) individuals . According to the Framingham equation , the 10-year risk of CVD was higher in SCP participants than in controls ( 11.2 % versus 8.5 % , P=0.06 ) . At termination of the SCP , 17/34 ( 50 % ) individuals had stopped smoking compared with 57/383 ( 15 % ) controls . Self-reported smoking abstinence for a12 months was 13/34 ( 38 % ) in the intervention group and 27/383 ( 7 % ) in the control group ( odds ration 6.2 , 95 % confidence interval 2.8 - 14.3 ) . During the follow-up , two SCP participants and 4 controls experienced a myocardial infa rct ion . One patient in the control group died of CVD . CONCLUSIONS SCP in HIV-infected individuals is feasible and should be encouraged . The long-term impact of smoking cessation on CVD morbidity and mortality should be evaluated in comparative trials Women are less successful than men at quitting smoking . We examined whether the male vs. female cessation outcome was influenced by baseline smoking behavior in participants who attempted to quit by using nicotine inhaler ( NI ) plus nicotine patch ( NP ) combination therapy . This double-blind , r and omized , placebo-controlled trial enrolled 196 men and 204 women . Group 1 ( 99 men , 101 women ) received NI plus NP ( 15 mg nicotine/16 h ) for 6 weeks , then NI plus placebo patch ( PP ) for 6 weeks , then NI alone for 14 weeks . Group 2 ( 97 men , 103 women ) received NI plus PP for 12 weeks , then NI alone for 14 weeks . Outcome measures were continuous self-reported abstinence and expired carbon monoxide concentration < 10 ppm . Baseline nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence ( FTND ) , and behavioral dependence by the 18- question Glover-Nilsson Smoking Behavioral Question naire ( GN-SBQ ) . Male vs. female complete abstinence rates , regardless of treatment group , were 61.7 % vs. 46.6 % at 6 weeks ( p = .0022 ) , 42.3 % vs. 30.9 % at 12 weeks ( p = .017 ) , 30.1 % vs. 17.6 % at 6 months ( p = .003 ) , and 23.0 % vs. 10.8 % at 12 months , respectively ( p = .001 ) . Men had significantly higher baseline FTND ( p = .0180 ) and lower total GN-SBQ ( p < .0001 ) scores than women . In conclusion , women appear to have higher behavioral , and lower nicotine , dependence than men according to the GN-SBQ and the FTND ; thus both nicotine and behavioral treatment should be tailored to women to increase their chances of abstinence The aim of this study was to describe smoking prevalence and smoking behavior in a multiethnic low-income HIV/AIDS population . A cross-sectional survey design was used . The study site was Thomas Street Clinic , an HIV/AIDS care facility serving a medically indigent and ethnically diverse population . Demographic , disease status , behavioral , and psychosocial variables were assessed by participant self-report . Surveys were collected from 348 study participants . Demographic composition of the sample was 78 % male , 25 % White , 44 % Black , and 29 % Hispanic . Study participants had a mean age of 40.2 years ( SD=7.8 ) . The HIV exposure profile of the sample was diverse : 46 % men who have sex with men , 35 % heterosexual contact , and 11 % injection drug use . Prevalence of current cigarette smoking in the sample was 46.9 % . Among participants with a lifetime history of smoking 100 or more cigarettes ( 62.8 % ) , only 26.6 % were currently abstinent , lower than the 48.8 % rate seen in the general population . Multiple logistic regression analysis indicated that race/ethnicity , education level , age , and heavy drinking were significantly associated with smoking status . Hispanics were less likely than Whites were to smoke , younger participants were less likely than older participants were to be current smokers , and heavy drinkers were more likely to be current smokers than were those who were not heavy drinkers . As education level increased , the likelihood of smoking decreased and the likelihood of quitting increased . The high smoking prevalence in this HIV/AIDS population demonstrates the need for smoking cessation interventions targeted to the special needs of this patient group INTRODUCTION PLHIV have higher rates of smoking and lower motivation to quit smoking ; thus to impact smoking rates , cessation interventions need to be acceptable to a wider range of PLHIV smokers as well as feasible to implement in a busy clinical setting . The purpose of this study was to evaluate the acceptability , feasibility , and effects of a Screening , Brief Intervention , and Referral for Treatment ( SBIRT ) model in an HIV/AIDS clinic among a sample of PLHIV . METHODS PLHIV smokers ( N=40 ) were r and omized at baseline , irrespective of their self-reported discrete smoking cessation motivation status , to receive either 8-weeks of combination nicotine replacement therapy ( NRT ) in conjunction with brief counseling ( SBIRT framework ) ( n=23 ) or usual care ( n=17 ) . Smoking outcome measures included cigarettes smoked per day , nicotine dependence , smoking urge , and smoking withdrawal symptoms . RESULTS The SBIRT intervention appeared to be acceptable and feasible , and produced medium to large reductions in cigarettes smoked per day , physical nicotine dependence , smoking urge , and smoking withdrawal symptoms , even for smokers not ready to quit within 6months . CONCLUSIONS Findings provide preliminary support for the integration of an SBIRT model in an HIV/AIDS clinic setting to screen and provide active treatment to all smokers , regardless of readiness to quit smoking . Given the high prevalence and incredible health burden of continued smoking in this population , identifying brief and effective interventions that are easily translated into clinical practice represents an enormous challenge that if met , will yield significant improvements to overall patient outcomes Background : Persons living with HIV are at increased risk for cardiovascular disease in part because of persistent inflammation and coagulation activation . Methods : We examined whether smoking and heavy episodic alcohol use ( defined as 5 or more drinks on one occasion ) were associated with greater monocyte activation ( soluble CD14 ) and coagulation ( D-dimer ) in participants in the Study to Underst and the Natural History of HIV and AIDS in the Era of Effective Therapy ( the “ SUN ” Study ) , a prospect i ve observational cohort . Results : Using regression analysis ( n = 689 ) , current smoking compared with nonsmoking was associated with significantly elevated soluble CD14 ( B = 135.57 , 95 % confidence interval : 84.95 to 186.19 , P < 0.001 ) , whereas heavy alcohol use compared with nonheavy use was associated with significantly lower D-dimer levels ( B = −0.059 , 95 % confidence interval : −0.102 to −0.016 , P = 0.007 ) . Conclusions : Smoking cessation should be encouraged by HIV care providers to improve mortality outcomes from all causes of death , particularly cardiovascular disease BACKGROUND While the detrimental effects of smoking among HIV-positive patients have been well documented , there is a paucity of data regarding cigarette smoking prevalence among these patients in South Africa ( SA ) . OBJECTIVES To establish the frequency , demographics , knowledge of harmful effects , and knowledge of smoking cessation strategies among HIV-positive patients in Johannesburg , SA . METHODS We conducted a prospect i ve cross-sectional survey using a structured question naire to interview HIV-positive patients attending the HIV Clinic at the Charlotte Maxeke Johannesburg Academic Hospital between 1 July and 31 October 2011 . RESULTS Of 207 HIV-positive patients attending an antiretroviral therapy ( ART ) roll-out clinic , 31 ( 15 % ) were current smokers ( 23.2 % of males and 7.4 % of females ) and a further 45 ( 21.7 % ) were ex-smokers . Most of the current smokers ( 30/31 patients ) indicated their wish to quit smoking , and among the group as a whole , most patients were aware of the general ( 82.1 % ) and HIV-related ( 77.8 % ) risks of smoking and of methods for quitting smoking . Despite this , however , most ( 62.3 % ) were not aware of who they could approach for assistance and advice . CONCLUSIONS Given the relatively high prevalence of current and ex-smokers among HIV-positive patients , there is a need for the introduction of smoking-cessation strategies and assistance at ART roll-out clinics in SA Because effects of cigarette smoking on health-related quality of life ( HRQL ) have not been well described , we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus ( MOS-HIV question naire ) in 585 HIV-infected homosexual/bisexual men , injection drug users , and female partners enrolled in a multicenter , prospect i ve study of the pulmonary complications of HIV infection . Mean scores for the following dimensions of HRQL were calculated : general health perception , quality of life , physical functioning , bodily pain , social functioning , role functioning , energy , cognitive functioning , and depression . A multivariate model was used to determine the impact on HRQL of the following factors : smoking , CD4 loss , acquired immune deficiency syndrome ( AIDS ) diagnoses , number of symptoms , study site , education , injection drug use , gender , and age . Current smoking was independently associated with lower scores for general health perception , physical functioning , bodily pain , energy , role functioning , and cognitive functioning ( all with p < 0.05 ) . We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers . These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes Abstract Background and objectives : Cardiovascular disease is a major concern in HIV-infected patients . Lifetime risk estimations use the risk of developing it over the course of remaining lifetime , and are useful in communicating this risk to young patients . We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain , and to estimate their lifetime risk of cardiovascular disease . Methods : Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain . Lifetime risk assessed according to Barry was classified in two major categories : low and high lifetime risk . Results : We included 895 subjects , 72 % men , median age 45.7 years ; median CD4 lymphocyte count 598 cells/μl , median time since HIV diagnosis 11 years , median time on antiretroviral treatment 6.3 years , 87 % had undetectable HIV viral load . Tobacco smoking was the most frequent risk factor ( 54 % ) , followed by dyslipidemia ( 48.6 % ) and hypertension ( 38.6 % ) . Estimated 10-year coronary risk ( Framingham/Regicor Risk Score ) risk was low ( < 5 % ) in 78 % of the patients , and intermediate ( 5–10 % ) in 20 % . Lifetime risk estimation showed a high risk profile for 71.4 % of the population studied , which was associated with increasing age , prolonged antiretroviral therapy and patient 's place of origin . Conclusions : Modifiable cardiovascular risk factors in this population are very common . There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy . A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable |
476 | 27,392,430 | Discussion This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking . | Background Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed .
Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol .
However , there has been little evaluation of the effectiveness of existing smartphone interventions .A systematic review , amongst other method ologies , identified promising modular content that could be delivered by an app : self-monitoring and feedback ; action planning ; normative feedback ; cognitive bias re-training ; and identity change .
This protocol reports a factorial r and omised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption . | This study aim ed to replicate findings that alcohol consumption and positive implicit beer-related cognitions can be reduced using inhibitory control ( IC ) training , with the addition of an active training control . Frontal EEG asymmetry , an objective psychophysiological index of approach motivation , was used as a dependent measure to examine training outcomes . Participants were r and omly assigned to one of two IC training conditions ( Beer NoGo or Beer Go ) or a Brief Alcohol Intervention ( BAI ) ( i.e. the active training control ) . The IC training tasks consistently paired a stimulus that required a response with images of water ( Beer NoGo ) or images of beer ( Beer Go ) . Alcohol consumption and implicit beer-related cognitions were measured at pre-training , post-training and at one week follow-up . Frontal EEG asymmetry was recorded during a passive image viewing task that presented neutral , healthy , and beer stimuli - at pre-training , post-training and follow-up . Participants in the Beer NoGo and BAI conditions consumed less beer in a taste test immediately after training than Beer Go participants , suggesting that IC training may be as effective as the already established BAI . The taste test findings were in line with the frontal EEG asymmetry data , which indicated that approach motivation for beer stimuli was altered in the expected directions . However , the positive correlation between post-training frontal EEG asymmetry data and taste test consumption was not significant . While there were no significant changes in implicit beer-related cognitions following training , a trending positive relationship between implicit beer-related cognitions at post-training and taste test consumption was reported . Further exploration addressing the limitations of the current study is required in order to clarify the implication s of these findings OBJECTIVE Alcohol screening and brief intervention ( SBI ) has gained widespread acceptance as an effective method for reducing problem drinking in at-risk population s. This study examines the cost and cost-effectiveness of an SBI pilot program delivered in an inner-city hospital emergency department ( ED ) to a traditionally underserved population . METHOD A total of 1,036 subjects were screened for problem drinking during their visit to an ED . Eligible participants ( N = 294 ) were r and omly assigned to either a brief intervention group or a control group . As the result of attrition , a final sample of 194 ( 90 brief intervention ; 104 control ) participants remained at follow-up . The intervention consisted of a brief counseling session and a health information packet . The control group received only the packet . Intervention cost data were collected and analyzed using the Drug Abuse Treatment Cost Analysis Program . Selected outcomes at the 3-month follow-up included the raw Alcohol Use Disorders Identification Test score , average weekly number of drinks and engaging in heavy drinking in the past month ( > 6 drinks on one occasion for men , > 4 for women ) . Outcome differences between the intervention and control groups were estimated with both bivariate and multivariate techniques . RESULTS The average economic cost of the brief intervention was dollars 632 per subject , of which screening ( dollars 497 ) was the largest component . In all cases , intervention subjects had better 3-month outcomes than control subjects , but the differences were not always statistically significant . Cost-effectiveness ratios were relatively small for all three outcomes , suggesting this type of intervention has the potential to be cost-effective under full implementation . CONCLUSIONS The preliminary results demonstrate the potential advantage of further research in this area with larger sample s and a longer follow-up period Background Excessive alcohol consumption has been linked to deleterious health consequences among undergraduate students . There is a need to develop theory-based and cost-effective brief interventions to attenuate alcohol consumption in this population . Purpose The present study tested the effectiveness of an integrated theory-based intervention in reducing undergraduates ' alcohol consumption in excess of guideline limits in national sample s from Estonia , Finl and , and the UK . Method A 2 ( volitional : implementation intention vs. no implementation intention ) × 2 ( motivation : mental simulation vs. no mental simulation ) × 3 ( nationality : Estonia vs. Finl and vs. UK ) r and omized-controlled design was adopted . Participants completed baseline psychological measures and self-reported number of alcohol units consumed and binge-drinking frequency followed by the intervention manipulation . One month later , participants completed follow-up measures of the psychological variables and alcohol consumption . Results Results revealed main effects for implementation intention and nationality on units of alcohol consumed at follow-up and an implementation intention × nationality interaction . Alcohol consumption was significantly reduced in the implementation intention condition for the Estonian and UK sample s. There was a significant main effect for nationality and an implementation intention × nationality interaction on binge-drinking frequency . Follow-up tests revealed significant reductions in binge-drinking occasions in the implementation intention group for the UK sample only . Conclusion Results support the implementation intention component of the intervention in reducing alcohol drinking in excess of guideline limits among Estonian and UK undergraduates . There was no support for the motivational intervention or the interaction between the strategies . Results are discussed with respect to intervention design based on motivational and volitional approaches Background Brief interventions via the internet have been shown to reduce university students ’ alcohol intake . This study tested two smartphone applications ( apps ) targeting drinking choices on party occasions , with the goal of reducing problematic alcohol intake among Swedish university students . Methods Students were recruited via e-mails sent to student union members at two universities . Those who gave informed consent , had a smartphone , and showed risky alcohol consumption according to the Alcohol Use Disorders Identification Test ( AUDIT ) were r and omized into three groups . Group 1 had access to the Swedish government alcohol monopoly ’s app , Promillekoll , offering real-time estimated blood alcohol concentration ( eBAC ) calculation ; Group 2 had access to a web-based app , PartyPlanner , developed by the research group , offering real-time eBAC calculation with planning and follow-up functions ; and Group 3 participants were controls . Follow-up was conducted at 7 weeks . Results Among 28574 students offered participation , 4823 agreed to join ; 415 were excluded due to incomplete data , and 1932 fulfilled eligibility criteria for r and omization . Attrition was 22.7–39.3 percent , higher among heavier drinkers and highest in Group 2 . Self-reported app use was higher in Group 1 ( 74 % ) compared to Group 2 ( 41 % ) . Per- protocol analyses revealed only one significant time-by-group interaction , where Group 1 participants increased the frequency of their drinking occasions compared to controls ( p = 0.001 ) . Secondary analyses by gender showed a significant difference among men in Group 1 for frequency of drinking occasions per week ( p = 0.001 ) , but not among women . Among all participants , 29 percent showed high-risk drinking , over the recommended weekly drinking levels of 9 ( women ) and 14 ( men ) st and ard glasses . Conclusions Smartphone apps can make brief interventions available to large numbers of university students . The apps studied using eBAC calculation did not , however , seem to affect alcohol consumption among university students and one app may have led to a negative effect among men . Future research should : 1 ) explore ways to increase user retention , 2 ) include apps facilitating technical manipulation for evaluation of added components , 3 ) explore the effects of adapting app content to possible gender differences , and 4 ) offer additional interventions to high-risk users . Trial registration clinical trials.gov : NCT01958398 Background Web-based tailored interventions provide users with information that is adapted to their individual characteristics and needs . R and omized controlled trials assessing the effects of tailored alcohol self-help programs among adults are scarce . Furthermore , it is a challenge to develop programs that can hold respondents ’ attention in online interventions . Objective To assess whether a 3-session , Web-based tailored intervention is effective in reducing alcohol intake in high-risk adult drinkers and to compare 2 computer-tailoring feedback strategies ( alternating vs summative ) on behavioral change , dropout , and appreciation of the program . Methods A single-blind r and omized controlled trial was conducted with an experimental group and a control group ( N=448 ) in Germany in 2010 - 2011 . Follow-up took place after 6 months . Drinking behavior , health status , motivational determinants , and demographics were assessed among participants recruited via an online access panel . The experimental group was divided into 2 subgroups . In the alternating condition ( n=132 ) , the tailored feedback was split into a series of messages discussing individual topics offered while the respondent was filling out the program . Participants in the summative condition ( n=181 ) received all advice at once after having answered all questions . The actual texts were identical for both conditions . The control group ( n=135 ) only filled in 3 question naires . To identify intervention effects , logistic and linear regression analyses were conducted among complete cases ( n=197 ) and after using multiple imputation . Results Among the complete cases ( response rate : 197/448 , 44.0 % ) who did not comply with the German national guideline for low-risk drinking at baseline , 21.1 % of respondents in the experimental group complied after 6 months compared with 5.8 % in the control group ( effect size=0.42 ; OR 2.65 , 95 % CI 1.14 - 6.16 , P=.02 ) . The experimental group decreased by 3.9 drinks per week compared to 0.4 drinks per week in the control group , but this did not reach statistical significance ( effect size=0.26 ; beta=−0.12 , 95 % CI −7.96 to 0.03 , P=.05 ) . Intention-to-treat analyses also indicated no statistically significant effect . Separate analyses of the 2 experimental subgroups showed no differences in intervention effects . The dropout rate during the first visit to the intervention website was significantly lower in the alternating condition than in the summative condition ( OR 0.23 , 95 % CI 0.08 - 0.60 , P=.003 ) . Program appreciation was comparable for the 2 experimental groups . Conclusions Complete case analyses revealed that Web-based tailored feedback can be an effective way to reduce alcohol intake among adults . However , this effect was not confirmed when applying multiple imputations . There was no indication that one of the tailoring strategies was more effective in lowering alcohol intake . Nevertheless , the lower attrition rates we found during the first visit suggest that the version of the intervention with alternating questions and advice may be preferred . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 91623132 ; http://www.controlled-trials.com/IS RCT N91623132 ( Archived by WebCite at http://www.webcitation.org/6J4QdhXeG ) BACKGROUND Alcoholism is a progressive neurocognitive developmental disorder . Recent evidence shows that computerized training interventions ( Cognitive Bias Modification , CBM ) can reverse some of these maladaptively changed neurocognitive processes . A first clinical study of a CBM , called alcohol-avoidance training , found that trained alcoholic patients showed less relapse at one-year follow-up than control patients . The present study tested the replication of this result , and questions about mediation and moderation . METHODS 509 alcohol-dependent patients received treatment as usual ( primarily Cognitive Behavior Therapy ) inpatient treatment . Before and after treatment , the implicit approach bias was measured with the Alcohol Approach-Avoidance Task . Half of the patients were r and omly assigned to CBM , the other half received treatment as usual only . Background variables , psychopathology and executive control were tested as possible moderating variables of CBM . One year after treatment , follow-up data about relapse were collected . RESULTS The group receiving CBM developed alcohol-avoidance behavior and reported significantly lower relapse rates at one-year follow-up . Change in alcohol-approach bias mediated this effect . Moderation analyses demonstrated that older patients and patients with a strong approach-bias at pretest profited most from CBM . CONCLUSIONS CBM is a promising treatment add-on in alcohol addiction and may counter some of the maladaptive neurocognitive effects of long-term alcoholism AIMS To test whether an expectancy challenge ( EC ) changes implicit and explicit alcohol-related cognitions and binge drinking in young heavy drinkers . This is important for theoretical and practical reasons : the EC presents a critical test for the hypothesized mediational role of alcohol cognitions and the EC has been presented as a promising intervention to counter alcohol problems in heavy drinking youth . SETTING , PARTICIPANTS AND INTERVENTION : Ninety-two heavy drinking college and university students ( half women ) were assigned r and omly to the EC or control condition ( a sham alcohol experiment in the same bar-laboratory ) . MEASUREMENTS Explicit alcohol cognitions and alcohol use were assessed with paper- and -pencil measures . Alcohol use was assessed prior to the experiment and during a 1-month follow-up . Implicit alcohol-related cognitions were assessed with two versions of the Implicit Association Test ( IAT ) , adapted to assess implicit valence and arousal associations with alcohol . FINDINGS AND CONCLUSIONS The EC result ed in decreased explicit positive arousal expectancies in men and women alike . There was some evidence for a differential reduction in implicit arousal associations , but findings depended on the version of the IAT and on the scoring-algorithm used . In men ( but not in women ) there was a short-lived differential reduction in prospect i ve alcohol use ( significant in week 3 of the follow-up ) , and this reduction was partially mediated by the decrease in explicit positive arousal expectancies . These findings suggest that an EC successfully changes explicit alcohol cognitions and that this may have short-lived beneficial effects in heavy drinking young men OBJECTIVE The current study examined the efficacy of mailed personalized normative feedback ( PNF ) as a brief alcohol intervention for at-risk college drinkers , and investigated discrepancy as a possible mediator of the intervention effect . METHOD Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline , 6-week posttest and 6-month follow-up . Measures included number of drinks consumed per heaviest drinking week , frequency of heavy-drinking episodes , peak blood alcohol concentration and number of alcohol-related problems , all for the last month . Participants were r and omly assigned to either a mailed brief intervention ( MBI ; n = 49 ) or attention-control ( C ; n = 51 ) group . The MBI group received mailed PNF that was based on baseline responses to the drinking measures ; the C group received a psychoeducational brochure about alcohol . RESULTS Mixed-model , repeated measures ANOVAs were used to examine the effects of time , group and gender on discrepancy and the drinking variables . Following the intervention , the MBI group reported significantly higher perceived discrepancy between self and others ' drinking than the C group . The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest ; however , these differences were no longer evident at the 6-month follow-up . Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy . CONCLUSIONS Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers OBJECTIVE This study compared a motivational intervention based on protection motivation theory ( PMT , Rogers , 1975 , 1983 ) with the same motivational intervention augmented by a volitional intervention based on implementation intentions ( Gollwitzer , 1993 ) . DESIGN The study had a longitudinal design , involving three waves of data collection over a 2-week period , incorporating an experimental manipulation of PMT variables at Time 1 and a volitional , implementation intention intervention at Time 2 . METHOD Participants ( N=248 ) were r and omly allocated to a control group or one of two intervention groups . Cognitions and exercise behaviour were measured at three time-points over a 2-week period . RESULTS The motivational intervention significantly increased threat and coping appraisal and intentions to engage in exercise but did not bring about a significant increase in subsequent exercise behaviour . In contrast , the combined protection motivation theory/implementation intention intervention had a dramatic effect on subsequent exercise behaviour . This volitional intervention did not influence behavioural intention or any other motivational variables . CONCLUSIONS It is concluded that supplementing PMT with implementation intentions strengthens the ability of the model to explain behaviour . This has implication s for health education programmes , which should aim to increase both participants ' motivation and their volition Background To evaluate the slightly modified version of the web-based brief alcohol intervention “ What Do You Drink ” ( WDYD ) among heavy drinking adolescents and young adults aged 15–20 years with a low educational background at one and six months follow-up . Methods A two-arm parallel group cluster r and omized controlled trial was conducted online in the Netherl and s in 2011–2012 . Participants included in the trial were recruited from preparatory and secondary vocational education institutions and had to be between 15 and 20 years of age and report heavy drinking in the past six months . In total , 73 classes representing 609 ( 59.9 % male ) participants were allocated to the experimental condition ( 37 classes , 318 participants : WDYD intervention ) or control condition ( 36 classes , 291 participants : no intervention ) . Outcomes were heavy drinking , weekly alcohol consumption , and frequency of binge drinking . Results Regressions analyses revealed no significant main intervention effects on any of the alcohol outcomes at one and six month ’s follow-up according to the intention-to-treat principle . Additionally , there were no moderating effects of gender , age , educational level , and readiness to change on the relation between the WDYD intervention and the alcohol outcomes at follow-up . Conclusions The WDYD intervention was not effective in reducing alcohol consumption among heavy drinking adolescents and young adults aged 15–20 years with a low educational background at one and six months follow-up . However , the absence of intervention effectiveness can not be used as an argument for not conducting these types of interventions with low educated individuals , since our study was the first to target this population .Trial registration Netherl and s Trial Register Background This paper reports the results of a pilot r and omized controlled trial comparing the delivery modality ( mobile phone/tablet or fixed computer ) of a cognitive behavioural therapy intervention for the treatment of depression . The aim was to establish whether a previously vali date d computerized program ( The Sadness Program ) remained efficacious when delivered via a mobile application . Method 35 participants were recruited with Major Depression ( 80 % female ) and r and omly allocated to access the program using a mobile app ( on either a mobile phone or iPad ) or a computer . Participants completed 6 lessons , weekly homework assignments , and received weekly email contact from a clinical psychologist or psychiatrist until completion of lesson 2 . After lesson 2 email contact was only provided in response to participant request , or in response to a deterioration in psychological distress scores . The primary outcome measure was the Patient Health Question naire 9 ( PHQ-9 ) . Of the 35 participants recruited , 68.6 % completed 6 lessons and 65.7 % completed the 3-months follow up . Attrition was h and led using mixed-model repeated- measures ANOVA . Results Both the Mobile and Computer Groups were associated with statistically significantly benefits in the PHQ-9 at post-test . At 3 months follow up , the reduction seen for both groups remained significant . Conclusions These results provide evidence to indicate that delivering a CBT program using a mobile application , can result in clinical ly significant improvements in outcomes for patients with depression . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN OBJECTIVE : The goal of this study was to evaluate the impact of the Active Teen Leaders Avoiding Screen-time ( ATLAS ) intervention for adolescent boys , an obesity prevention intervention using smartphone technology . METHODS : ATLAS was a cluster r and omized controlled trial conducted in 14 secondary schools in low-income communities in New South Wales , Australia . Participants were 361 adolescent boys ( aged 12–14 years ) considered at risk of obesity . The 20-week intervention was guided by self-determination theory and social cognitive theory and involved : teacher professional development , provision of fitness equipment to schools , face-to-face physical activity sessions , lunchtime student mentoring sessions , research er-led seminars , a smartphone application and Web site , and parental strategies for reducing screen-time . Outcome measures included BMI and waist circumference , percent body fat , physical activity ( accelerometers ) , screen-time , sugar-sweetened beverage intake , muscular fitness , and resistance training skill competency . RESULTS : Overall , there were no significant intervention effects for BMI , waist circumference , percent body fat , or physical activity . Significant intervention effects were found for screen-time ( mean ± SE : –30 ± 10.08 min/d ; P = .03 ) , sugar-sweetened beverage consumption ( mean : –0.6 ± 0.26 glass/d ; P = .01 ) , muscular fitness ( mean : 0.9 ± 0.49 repetition ; P = .04 ) , and resistance training skills ( mean : 5.7 ± 0.67 units ; P < .001 ) . CONCLUSIONS : This school-based intervention targeting low-income adolescent boys did not result in significant effects on body composition , perhaps due to an insufficient activity dose . However , the intervention was successful in improving muscular fitness , movement skills , and key weight-related behaviors Aims : Heavy drinkers tend to overestimate how much others drink ( normative fallacy ) , at least in college sample s. Little research has been conducted to evaluate whether normative misperceptions about drinking extend beyond the college population . The present study explored normative misperceptions in an adult general population sample of drinkers . Methods : As part of a larger study , in Toronto , Canada , a r and om digit dialling telephone survey was conducted with 14,009 participants who drank alcohol at least once per month . Respondents with Alcohol Use Disorders Identification Test of eight or more ( n = 2757 ) were asked to estimate what percent of Canadians of their same sex : ( a ) drank more than they do ; ( b ) were abstinent and ( c ) drank seven or more drinks per week . Respondents ' estimates of these population drinking norms were then compared with the actual levels of alcohol consumption in the Canadian population . Results : A substantial level of normative misperception was observed for estimates of levels of drinking in the general population . Estimates of the proportion of Canadians who were abstinent were fairly accurate . There was some evidence of a positive relationship between the respondents ' own drinking severity and the extent of normative misperceptions . Little evidence was found of a relationship between degree of normative misperceptions and age . Conclusion : Normative misperceptions have been successfully targeted in social norms media campaigns as well as in personalized feedback interventions for problem drinkers . The present research solidifies the empirical bases for extending these interventions more widely into the general population Objective To evaluate the effectiveness of different brief intervention strategies at reducing hazardous or harmful drinking in primary care . The hypothesis was that more intensive intervention would result in a greater reduction in hazardous or harmful drinking . Design Pragmatic cluster r and omised controlled trial . Setting Primary care practice s in the north east and south east of Engl and and in London . Participants 3562 patients aged 18 or more routinely presenting in primary care , of whom 2991 ( 84.0 % ) were eligible to enter the trial : 900 ( 30.1 % ) screened positive for hazardous or harmful drinking and 756 ( 84.0 % ) received a brief intervention . The sample was predominantly male ( 62 % ) and white ( 92 % ) , and 34 % were current smokers . Interventions Practice s were r and omised to three interventions , each of which built on the previous one : a patient information leaflet control group , five minutes of structured brief advice , and 20 minutes of brief lifestyle counselling . Delivery of the patient leaflet and brief advice occurred directly after screening and brief lifestyle counselling in a subsequent consultation . Main outcome measures The primary outcome was patients ’ self reported hazardous or harmful drinking status as measured by the alcohol use disorders identification test ( AUDIT ) at six months . A negative AUDIT result ( score < 8) indicated non-hazardous or non-harmful drinking . Secondary outcomes were a negative AUDIT result at 12 months , experience of alcohol related problems ( alcohol problems question naire ) , health utility ( EQ-5D ) , service utilisation , and patients ’ motivation to change drinking behaviour ( readiness to change ) as measured by a modified readiness ruler . Results Patient follow-up rates were 83 % at six months ( n=644 ) and 79 % at 12 months ( n=617 ) . At both time points an intention to treat analysis found no significant differences in AUDIT negative status between the three interventions . Compared with the patient information leaflet group , the odds ratio of having a negative AUDIT result for brief advice was 0.85 ( 95 % confidence interval 0.52 to 1.39 ) and for brief lifestyle counselling was 0.78 ( 0.48 to 1.25 ) . A per protocol analysis confirmed these findings . Conclusions All patients received simple feedback on their screening outcome . Beyond this input , however , evidence that brief advice or brief lifestyle counselling provided important additional benefit in reducing hazardous or harmful drinking compared with the patient information leaflet was lacking . Trial registration Current Controlled Trials IS RCT N06145674 The authors evaluated the efficacy of a computer-delivered personalized normative feedback intervention in reducing alcohol consumption among heavy-drinking college students . Participants included 252 students who were r and omly assigned to an intervention or control group following a baseline assessment . Immediately after completing measures of reasons for drinking , perceived norms , and drinking behavior , participants in the intervention condition were provided with computerized information detailing their own drinking behavior , their perceptions of typical student drinking , and actual typical student drinking . Results indicated that normative feedback was effective in changing perceived norms and alcohol consumption at 3- and 6-month follow-up assessment s. In addition , the intervention was somewhat more effective at 3-month follow-up among participants who drank more for social reasons OBJECTIVE The aims of this study were to compare university students ' perceptions of drinking norms with actual student drinking norms , to examine the relationship between norm misperception and individual drinking status and to investigate the relative importance of three reference groups as potential determinants of individual drinking levels : young people in New Zeal and of the same age and gender , local university students of the same age and gender and the closest friends of individual respondents . METHOD In 2002 a r and omly selected representative sample of 1,564 New Zeal and university students aged 16 - 29 years completed an Internet-based survey of their alcohol use ( response rate : 82 % ) . Respondents were asked to estimate the incidence of heavy episodic drinking and vomiting in the three reference groups and to rate their own drinking in comparison . Estimates within + /- 10 % of actual norms were rated as accurate ; estimates above or below actual norms by more than 10 % were rated , respectively , as overestimates and underestimates . RESULTS The vast majority of women ( 80 % ) and men ( 73 % ) overestimated the incidence of heavy drinking among student peers . The incidence of vomiting was also overestimated , but to a lesser extent . The extents of overestimation for both heavy drinking and vomiting were strongly related to the individual 's heavy drinking frequency ( p < .001 ) . Only 9 % of drinkers believed they drank more than other students . Correlations of perceived norms and self-reported drinking increased with the proximity of the social grouping to the individual and were higher for women than for men . CONCLUSIONS This New Zeal and university sample showed strong evidence of norm misperceptions , consistent with the results of several U.S. studies . Perceived norms are strongly related to individual drinking levels . It is unclear whether norm misperceptions are a cause or effect of heavy drinking . Research in which norm misperceptions are corrected may assist in underst and ing their importance in the etiology and treatment of heavy drinking AIMS Previous research has shown that consistently not responding to alcohol-related stimuli in a go/no-go training procedure reduces drinking behaviour . This study aim ed to examine further the mechanisms underlying this go/no-go training effect . DESIGN , SETTING AND PARTICIPANTS Fifty-seven heavy drinkers were assigned r and omly to two training conditions : in the beer/no-go condition , alcohol-related stimuli were always paired with a stopping response , while in the beer/go condition participants always responded to alcohol-related stimuli . Participants were tested individually in a laboratory at Maastricht University . MEASUREMENTS Weekly alcohol intake , implicit attitudes towards beer , approach-avoidance action tendencies towards beer and response inhibition were measured before and after the training . FINDINGS Results showed a significant reduction in both implicit attitudes ( P = 0.03 ) and alcohol intake ( P = 0.02 ) in the beer/no-go condition , but not in the beer/go condition . There were no significant training effects on action tendencies or response inhibition . CONCLUSIONS Repeatedly stopping pre-potent responses towards alcohol-related stimuli reduces excessive alcohol use via a devaluation of alcohol-related stimuli rather than via increased inhibitory control over alcohol-related responses OBJECTIVE To test the effectiveness of implementation intentions to decrease alcohol consumption and control for possible dem and characteristics by employing an active control condition and contrasting experimenter-provided with self-generated implementation intentions . DESIGN Two hundred forty-eight participants were r and omly allocated to 1 of 4 conditions : question naire-only ; question naire plus planning instruction ; question naire , planning instruction plus experimenter-provided implementation intention ; or question naire , planning instruction plus self-generated implementation intention . MAIN OUTCOME MEASURE Alcohol intake . RESULTS There were clinical ly and statistically significant decreases in alcohol consumption in the 2 experimental conditions , but not in the 2 control conditions , F(3 , 237 ) = 3.34 , p < .05 , etap(2 ) = .04 . There were no significant differences between experimenter-provided and self-generated implementation intentions ( p = .62 ) . Compliance moderated the effects of self-generated implementation intentions only , such that alcohol intake only significantly decreased in participants who complied with the instructions , F(1 , 52 ) = 4.20 , p < .05 , etap(2 ) = .07 . However , simply choosing an experimenter-provided implementation intention was just as effective as writing it out in full , implying that implementation intentions work even with minimal information processing . CONCLUSION The findings further support use of implementation intentions to protect against health risk behaviors and are congruent with laboratory research showing that implementation intentions are a case of strategic automaticity OBJECTIVE As many as one in four adults in North America experiences some problems due to alcohol consumption . Although most of these problem drinkers do not have concerns that are severe enough to merit formal treatment , such drinking has large economic costs and can place the drinker at risk for long-term negative health and social consequences . The present study evaluated a minimal intervention that used normative feedback about population drinking to motivate changes in alcohol use . METHOD An intervention pamphlet was mailed to over 6,000 households in Toronto , r and omized by block from a region containing almost 10,000 households . In the month after the mailing , a general population survey was conducted in the region to assess alcohol use . RESULTS Respondents from households receiving normative feedback ( n = 472 ) reported significantly lower alcohol use than controls ( n = 225 ) , but this effect occurred only among respondents who met an objective criterion for problem drinking and who perceived some risk associated with their drinking . CONCLUSIONS Viewed from a public health perspective , normative feedback interventions have the potential for a significant payoff because they can be provided at low cost and to problem drinkers who might ordinarily never access any treatment services A new training to decrease attentional bias ( attentional bias modification training , ABM ) was tested in a r and omized controlled experimental study with alcohol-dependent patients as an addition to cognitive behavioral therapy . In alcohol dependence , attentional bias has been associated with severity of alcoholism , craving , treatment outcome , and relapse . Forty-three patients with DSM-IV diagnosis of alcohol dependence were r and omly assigned to an ABM intervention or control training . The procedure consisted of five sessions in which patients were trained to disengage attention from alcohol-related stimuli ( ABM condition ) or in which they were trained on an irrelevant reaction-time test ( control condition ) . We measured the effects of ABM on the visual-probe task , with stimuli that were presented in the ABM and with new stimuli . Craving was measured with the Desires for Alcohol Question naire . Follow-up data were gathered for overall treatment success , and relapse up to 3 months after the intervention . ABM was effective in increasing the ability to disengage from alcohol-related cues . This effect generalized to untrained , new stimuli . There were no significant effects on subjective craving . For other outcome measures there were indications of clinical ly relevant effects . Results indicate that ABM among alcohol-dependent patients was effective and that it may affect treatment progression . Large-scale trials are warranted to further investigate this new field In this article two new methods for building and evaluating eHealth interventions are described . The first is the Multiphase Optimization Strategy ( MOST ) . It consists of a screening phase , in which intervention components are efficiently identified for inclusion in an intervention or for rejection , based on their performance ; a refining phase , in which the selected components are fine tuned and issues such as optimal levels of each component are investigated ; and a confirming phase , in which the optimized intervention , consisting of the selected components delivered at optimal levels , is evaluated in a st and ard r and omized controlled trial . The second is the Sequential Multiple Assignment R and omized Trial ( SMART ) , which is an innovative research design especially suited for building time-varying adaptive interventions . A SMART trial can be used to identify the best tailoring variables and decision rules for an adaptive intervention empirically . Both the MOST and SMART approaches use r and omized experimentation to enable valid inferences . When properly implemented , these approaches will lead to the development of more potent eHealth interventions According to dual-process models , excessive alcohol use emerges when response inhibition ability is insufficient to inhibit automatic impulses to drink alcohol . This study examined whether strengthening response inhibition for alcohol-related cues decreases alcohol intake . Fifty-two heavy drinking students were r and omly assigned to one of two conditions : In the beer/no-go condition , participants performed a go/no-go task that consistently paired alcohol-related stimuli with a stopping response , to increase response inhibition for alcohol-related stimuli . In the beer/go condition , in contrast , participants were always required to respond to alcohol-related stimuli during the go/no-go task . Before and after the go/no-go manipulation , we measured weekly alcohol intake and implicit attitudes toward alcohol . In addition , we measured alcohol consumption during a taste test immediately after the go/no-go manipulation . Following the manipulation , participants in the beer/no-go condition demonstrated significantly increased negative implicit attitudes toward alcohol , and a significant reduction in weekly alcohol intake , while participants in the beer/go condition showed a non-significant increase in implicit positive attitudes toward alcohol and a significant increase in weekly alcohol intake . This study demonstrates that repeatedly stopping prepotent responses toward alcohol-related stimuli can be an effective strategy to reduce excessive alcohol use Although behavior modification of obesity is usually described as a behavior change procedure , measurement is most often limited to the outcome variable of weight loss . The present investigation employed detailed behavior monitoring forms in half of 16 obesity groups ( n = 173 ) matched across four different therapists . The percentage of compliance for nine specific treatment behaviors was charted from these monitoring forms . At the end of treatment , the eight groups that had the behavior monitoring treatment averaged over 6 pounds more weight lost than the matched control groups as well as showing significantly better attendance . The between group weight loss differences were still evident 3 months after treatment AIMS The main aim of this study was to test whether automatic action-tendencies to approach alcohol can be modified , and whether this affects drinking behaviour . DESIGN AND PARTICIPANTS Forty-two hazardous drinkers were assigned r and omly to a condition in which they were implicitly trained to avoid or to approach alcohol , using a training variety of the alcohol Approach Avoidance Test ( AAT ) . Participants pushed or pulled a joystick in response to picture-format ( l and scape or portrait ) . The pictures depicted alcoholic or non-alcoholic drinks . Participants in the avoid-alcohol condition pushed most alcoholic and pulled most non-alcoholic drinks . For participants in the approach-alcohol condition these contingencies were reversed . After the implicit training , participants performed a taste test , including beers and soft drinks . Automatic action tendencies at post-test were assessed with the AAT , including both trained and untrained pictures , and with a different test ( Implicit Association Test , IAT ) . We further tested effects on subjective craving . RESULTS Action tendencies for alcohol changed in accordance with training condition , with the largest effects in the clinical ly relevant avoid-alcohol condition . These effects occurred outside subjective awareness and generalized to new pictures in the AAT and to an entirely different test using words , rather than pictures ( IAT ) . In relatively heavy drinking participants who demonstrated changed action tendencies in accordance with their training condition , effects were found on drinking behaviour , with participants in the approach-alcohol condition drinking more alcohol than participants in the avoid-alcohol condition . No effect was found on subjective craving . CONCLUSIONS Retraining automatic processes may help to regain control over addictive impulses , which points to new treatment possibilities AIMS To examine whether alcohol-related attentional bias ( AB ) can be reduced by training heavy drinkers to attend to soft drinks as an alternative to alcohol . Diminishing AB is important because AB has been suggested to be a significant factor in the development , maintenance and relapse of addictive behaviours . AB was trained in a clinical ly relevant design , and we studied the generalization of this training . DESIGN , PARTICIPANTS AND INTERVENTION : We assigned r and omly 106 heavy drinking male college and university students to the attentional re-training ( AR ; modified visual-probe task ) or control condition ( st and ard visual-probe task ) . SETTING Laboratory at Maastricht University . MEASUREMENTS We measured the effects of AR on the visual-probe task with stimuli that were presented in the AR and with new stimuli , and on an alternative measure of AB , the flicker paradigm . We further measured effects on craving and preference for either an alcohol beverage or a soft drink . FINDINGS After AR , participants had learned to avoid alcohol stimuli and had developed an AB for soft drinks . This effect was restricted to stimuli used in the AR . The flicker task , where AB for alcohol was found in both the AR and control groups , was not affected by the AR . No effect was found on craving and the preference task . CONCLUSIONS Although heavy drinkers can learn to attend selectively to an alternative category for alcohol , a single AR is not sufficient to decrease symptoms of problem drinking BACKGROUND Physical inactivity is a major , potentially modifiable , risk factor for cardiovascular disease , cancer , and other chronic diseases . Effective , simple , and generalisable interventions that will increase physical activity in population s are needed . AIM To evaluate the effectiveness of a smartphone application ( app ) to increase physical activity in primary care . DESIGN AND SETTING An 8-week , open-label , r and omised controlled trial in rural , primary care in the west of Irel and . METHOD And roid smartphone users > 16 years of age were recruited . All participants were provided with similar physical activity goals and information on the benefits of exercise . The intervention group was provided with a smartphone app and detailed instructions on how to use it to achieve these goals . The primary outcome was change in physical activity , as measured by a daily step count between baseline and follow-up . RESULTS A total of 139 patients were referred by their primary care health professional or self-referred . In total , 37 ( 27 % ) were screened out and 12 ( 9 % ) declined to participate , leaving 90 ( 65 % ) patients who were r and omised . Of these , 78 provided baseline data ( intervention = 37 ; control = 41 ) and 77 provided outcome data ( intervention = 37 ; control = 40 ) . The mean daily step count at baseline for intervention and control groups was 4365 and 5138 steps per day respectively . After adjusting , there was evidence of a significant treatment effect ( P = 0.009 ) ; the difference in mean improvement in daily step count from week 1 to week 8 inclusive was 1029 ( 95 % confidence interval 214 to 1843 ) steps per day , favouring the intervention . Improvements in physical activity in the intervention group were sustained until the end of the trial . CONCLUSION A simple smartphone app significantly increased physical activity over 8 weeks in a primary care population BACKGROUND Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs ; however , long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites . We aim ed to assess a new interactive internet-based intervention ( StopAdvisor ) for smoking cessation that was design ed with particular attention directed to people with low socioeconomic status . METHODS We did this online r and omised controlled trial between Dec 6 , 2011 , and Oct 11 , 2013 , in the UK . Participants aged 18 years and older who smoked every day were r and omly assigned ( 1:1 ) to receive treatment with StopAdvisor or an information-only website . R and omisation was automated with an unseen r and om number function embedded in the website to establish which treatment was revealed after the online baseline assessment . Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status sub population s. Participants , and research ers who obtained data and did laboratory analyses , were masked to treatment allocation . The primary outcome was 6 month sustained , biochemically verified abstinence . The main secondary outcome was 6 month , 7 day biochemically verified point prevalence . Analysis was by intention to treat . Homogeneity of intervention effect across the socioeconomic sub sample s was first assessed to establish whether overall or separate sub sample analyses were appropriate . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N99820519 . FINDINGS We r and omly assigned 4613 participants to the StopAdvisor group ( n=2321 ) or the control group ( n=2292 ) ; 2142 participants were of low socioeconomic status and 2471 participants were of high status . The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary ( 237 [ 10 % ] vs 220 [ 10 % ] participants ; relative risk [ RR ] 1·06 , 95 % CI 0·89 - 1·27 ; p=0·49 ) and the secondary ( 358 [ 15 % ] vs 332 [ 15 % ] participants ; 1·06 , 0·93 - 1·22 ; p=0·37 ) outcomes ; however , the intervention effect differed across socioeconomic status sub sample s ( 1·44 , 0·99 - 2·09 ; p=0·0562 and 1·37 , 1·02 - 1·84 ; p=0·0360 , respectively ) . StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website ( primary outcome : 90 [ 8 % ] of 1088 vs 64 [ 6 % ] of 1054 participants ; RR 1·36 , 95 % CI 1·00 - 1·86 ; p=0·0499 ; secondary outcome : 136 [ 13 % ] vs 100 [ 10 % ] participants ; 1·32 , 1·03 - 1·68 , p=0·0267 ) , but did not improve cessation rates in those with high socioeconomic status ( 147 [ 12 % ] of 1233 vs 156 [ 13 % ] of 1238 participants ; 0·95 , 0·77 - 1·17 ; p=0·61 and 222 [ 18 % ] vs 232 [ 19 % ] participants ; 0·96 , 0·81 - 1·13 , p=0·64 , respectively ) . INTERPRETATION StopAdvisor was more effective than an information-only website in smokers of low , but not high , socioeconomic status . StopAdvisor could be implemented easily and made freely available , which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support . FUNDING National Prevention Research Initiative Efforts to reduce the frequency of high-risk drinking have included the use of motivational interventions . Both the technique used in motivational interventions and an underlying theory of behavior change ( i.e. , self-regulation theory ) invoke the construct of discrepancy development . This study was design ed to determine whether techniques purported to develop discrepancy actually do so and to compare methods of developing discrepancy on indices of intention to reduce alcohol use . Male and female college drinkers ( N=92 ) were selected if they reported two or more binge episodes in the last month , or scored 4 or higher on the Rutgers Alcohol Problem Index ( RAPI ) . Participants were r and omly assigned by gender to three conditions all conducted in a small group format : attention-control , personalized normative feedback ( PNF ) , and personal strivings assessment ( PSA ) . Personalized normative feedback was design ed to develop discrepancy based on behavioral comparisons of self and others . Personal strivings assessment was design ed to develop discrepancy between current and ideal self . It was hypothesized that participants who engage in discrepancy building activities would experience discrepancy specific to the activity in which they engaged , and that all participants who developed discrepancy would show higher levels of intention to reduce alcohol use . Results indicated that only the personalized normative feedback increased discrepancy and intention to reduce alcohol use BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant |
477 | 20,974,653 | Training health professionals by CST is a promising approach to change communication behaviour and attitudes . | OBJECTIVE Group training in communication skills [ communication skills training ( CST ) ] has become partly m and atory for oncology staff .
However , so far , a comprehensive meta- analysis on the efficacy is lacking .
DESIGN Included studies either compare the efficacy of a specific training with a control group or look at the additional effect of booster sessions on communication behaviour , attitudes or patient outcomes . | There is today a wide consensus regarding the need to improve communication skills ( CS ) of health-care professionals ( HCPs ) dealing with cancer patients . Psychological training programs ( PTPs ) may be useful to acquire the needed CS . Testing the efficacy of PTP will allow to define their optimal content . The present study was design ed to assess the impact of a PTP on HCP stress , attitudes and CS , and on HCP and patients ' satisfaction with HCP communication skills in a r and omised study . A total of 115 oncology nurses were r and omly assigned to a 105-h PTP or to a waiting list . Stress was assessed with the Nursing Stress Scale , attitudes with a Semantic Differential Question naire , CS used during one simulated and one actual patient interview with the Cancer Research Campaign Workshop Evaluation Manual , and satisfaction with the nurses ' CS with a question naire completed by the patients and the nurses . Trained ( TG ) and control ( CG ) groups were compared at baseline , after 3 months ( just following training for TG ) and after 6 months ( 3 months after the end of training for TG ) . Compared to controls , trained nurses reported positive changes on their stress levels ( P⩽0.05 ) and on their attitudes ( P⩽0.05 ) . Positive training effects were found on CS used during the simulated interview : a significant increase in facilitative behaviours ( open questions : P⩽0.001 ; evaluative functions : P⩽0.05 ) and a significant decrease in inhibitory behaviours ( inappropriate information : P⩽0.01 ; false reassurance : P⩽0.05 ) . Less positive training effects were found regarding interviews with a cancer patient : a significant increase in educated guesses ( P⩽0.001 ) was noticed . No training effect was observed on nurses ' satisfaction levels , but a positive training effect was found on patients ' satisfaction levels ( P⩽0.01 ) . Although results outline PTP efficacy , they indicate the need to design PTP , amplifying the transfer of learned CS to clinical practice PURPOSE We wanted to assess the effectiveness of intensive education for physicians compared with a traditional session on communicating with breast cancer patients . METHODS A r and omized controlled trial was conducted in practice s in London , Hamilton , and Toronto , Canada , with 17 family physicians , 16 surgeons , and 18 oncologists , and with 102 patients of the surgeons and oncologists . Doctors were r and omized to 1 of 2 continuing education approaches : a traditional 2-hour version ( control group ) , or a new 6-hour intensive version including exploring the patients ’ perspectives and review ing videotapes and receiving feedback ( intervention group ) . Communication behavior of the physicians was measured objective ly both before and after the intervention . As well , 4 postintervention patient outcomes were measured , by design only for surgeons and oncologists : patient-centerdness of the visit , satisfaction , psychological distress , and feeling better . RESULTS No significant differences were found on the communication score of the intervention vs the control physicians when controlling for preintervention communication scores . Intervention family physicians , however , had significantly higher communication subscores than control family physicians . Also , patients of the intervention surgeons and oncologists were significantly more satisfied ( scores of 82.06 vs 77.78 , P = .03 ) and felt better ( 88.2 % vs 70.6 % , P=.02 ) than patients of the control surgeons and oncologists when controlling for covariates and adjusting for clustering within doctor . CONCLUSIONS The continuing medical education intervention was effective in terms of some but not all physician and patient outcomes BACKGROUND No study has yet assessed the impact of physicians ' skills acquisition after a communication skills training programme on the evolution of patients ' anxiety following a medical consultation . This study aim ed to compare the impact , on patients ' anxiety , of a basic communication skills training programme ( BT ) and the same programme consoli date d by consolidation workshops ( CW ) , and to investigate physicians ' communication variables associated with patients ' anxiety . PATIENTS AND METHODS Physicians , after attending the BT , were r and omly assigned to CW or to a waiting list . The control group was not a non-intervention group . Consultations with a cancer patient were recorded . Patients ' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation . Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual . RESULTS No statistically significant change over time and between groups was observed . Mixed-effects modelling showed that a decrease in patients ' anxiety was linked with screening questions ( P = 0.045 ) , physicians ' satisfaction about support given ( P = 0.004 ) and with patients ' distress ( P < 0.001 ) . An increase in anxiety was linked with breaking bad news ( P = 0.050 ) and with supportive skills ( P = 0.013 ) . No impact of the training programme was observed . CONCLUSIONS This study shows the influence of some communication skills on the evolution of patients ' anxiety . Physicians should be aware of these influences The provision of adequate information in a clear and sensitive manner can improve cancer patients ' experience of care . Satisfaction with the cancer consultation may impact on satisfaction with care in general and adjustment to the disease . This study aims to identify factors that influence patient and clinician satisfaction with the cancer consultation and whether satisfaction can be improved with communication skills training . 160 doctors from 34 UK cancer centres participated . Half were r and omized to attend a communication skills training course . Patient satisfaction data are presented at baseline and following a communication skills course or in the case of the control doctors , three months after baseline . Clinicians also rated their satisfaction with the consultations . Overall patient satisfaction was not related to the speciality , seniority or sex of the clinician or patient , site of primary cancer or type of treatment . Satisfaction was related to patients ' age , psychological morbidity and , most significantly , satisfaction with the length of wait in clinic . Clinician satisfaction was not related to age , sex or cancer site but clinicians were less satisfied following consultations with patients being treated palliatively . Communication skills training had a non-significant positive effect on patient satisfaction . The subtle benefits of improved communication may be overshadowed by practical problems such as waiting too long to see the doctor , which have an adverse effect on satisfaction The emotional content of health care professionals – cancer patient communication is often considered as poor and has to be improved by an enhancement of health care professionals empathy . One hundred and fifteen oncology nurses participating in a communication skills training workshop were assessed at three different periods . Nurses r and omly allocated to a control group arm ( waiting list ) were assessed a first time and then 3 and 6 months later . Nurses allocated to the training group were assessed before training workshop , just after and 3 months later . Each nurse completed a 20-min clinical and simulated interview . Each interview was analysed by three content analysis systems : two computer-supported content analysis of emotional words , the Harvard Third Psychosocial Dictionary and the Martindale Regressive Imagery Dictionary and an observer rating system of utterances emotional depth level , the Cancer Research Campaign Workshop Evaluation Manual . The results show that in clinical interviews there is an increased use of emotional words by health care professionals right after having been trained ( P=0.056 ) : training group subjects use 4.3 ( std : 3.7 ) emotional words per 1000 used before training workshop , and 7.0 ( std : 5.8 ) right after training workshop and 5.9 ( std : 4.3 ) 3 months later compared to control group subjects which use 4.5 ( std : 4.8 ) emotional words at the first assessment point , 4.3 ( std : 4.1 ) at the second and 4.4 ( std : 3.3 ) at the third . The same trend is noticeable for emotional words used by health care professionals in simulated interviews ( P=0.000 ) . The emotional words registry used by health care professionals however remains stable over time in clinical interviews ( P=0.141 ) and is enlarged in simulated interviews ( P=0.041 ) . This increased use of emotional words by trained health care professionals facilitates cancer patient emotion words expressions compared to untrained health care professionals especially 3 months after training ( P=0.005 ) . This study shows that health care professionals empathy may be improved by communication skills training workshop and that this improvement facilitates cancer patients emotions expression PURPOSE Although it is widely recognised that educational interventions may be more effective for people with an ' internal ' Locus of Control ( who believe that life outcomes are controlled by their own characteristics or actions ) compared to people with an ' external ' Locus of Control ( who believe that life outcomes are controlled by external forces such as luck , fate or others ) , no study has yet assessed the influence of physicians ' Locus of Control ( LOC ) on communication skills learning . This study aims to test the hypothesis that , in a communication skills training program , physicians with an ' internal ' LOC would demonstrate communication skills acquisition to a greater degree than those with an ' external ' LOC . METHODS A non-r and omised longitudinal intervention study was conducted between January 1999 and April 2001 . Sixty-seven volunteer physicians from private and institutional practice in Belgium participated in a learner-centred , skills-focused , practice -oriented communication skills training program . Communication skills changes were assessed in 2 st and ardised simulated interviews before and after training ( one two-person and one three-person interview ) . Communication skills were assessed using the Cancer Research Campaign Workshop Evaluation Manual . Physicians ' LOC was assessed using the Rotter I-E scale . Communication skills changes of the upper and lower third of physicians in respect of their scores on this scale were compared using group by time repeated measures of variance . RESULTS In the two-person and three-person interviews , changes in the use of open directive questions were more important among physicians with an " internal " LOC compared with changes observed among physicians with an ' external ' LOC ( P=0.066 and P=0.004 , respectively ) . In the three-person interview , changes in the use of directive questions , assessing functions and moderate feelings stated explicitly were more important among physicians with an ' internal ' LOC compared with changes observed among physicians with an ' external ' LOC ( P= 0.001 ; P=0.002 and P=0.011 respectively ) . CONCLUSION This study shows that physicians ' LOC is a psychological characteristic that could influence the efficacy of a communication skills training program . This evidence supports the idea that a psychological characteristic such as ' internal ' LOC may facilitate communication skills acquisition through physicians ' belief that communication with patients may be controlled by physicians themselves BACKGROUND Doctors ' communication with patients is commonly hampered by lack of training in this core skill . This study aim ed to assess the efficacy of an intensive 3-day training course on communication skills in a r and omised controlled trial with a two-by-two factorial design and several outcomes . METHODS 160 oncologists from 34 UK cancer centres were r and omly allocated to four groups : written feedback followed by course ; course alone ; written feedback alone ; and control . At each of two assessment periods , consultations with six to ten consecutive , consenting patients per doctor were videotaped . 2407 patients participated . Outcome measures included objective and subjective ratings made by research ers , doctors , and patients . The primary outcomes were objective improvements after the intervention in key communication skills . Course content included structured feedback , videotape review of consultations , role-play with simulated patients , interactive group demonstrations , and discussion led by a trained facilitator . FINDINGS In Poisson regression analysis of counts of communication behaviours , course attendance significantly improved key outcomes . The estimated effect sizes corresponded to higher rates of use of focused questions ( difference between course attenders [ n=80 ] and non-attenders [ n=80 ] 34 % , p=0.003 ) , focused and open questions ( 27 % , p=0.005 ) , expressions of empathy ( 69 % , p=0.003 ) , and appropriate responses to patients ' cues ( 38 % , p=0.026 ) , and a 24 % lower rate of use of leading questions ( p=0.11 ) . There was little evidence for the effectiveness of written feedback . INTERPRETATION The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience . This trial shows that training courses significantly improve key communication skills . More re sources should be allocated to address doctors ' training needs in this vital area BACKGROUND No study has yet assessed the impact of physicians ' skills acquisition after a communication skills training program on changes in patients ' and relatives ' anxiety following a three-person medical consultation . This study aim ed at comparing , in a r and omized study , the impact , on patients ' and relatives ' anxiety , of a basic communication skills training program and the same program consoli date d by consolidation workshops and at investigating physicians ' communication variables associated with patients ' and relatives ' anxiety . METHODS Consultations with a cancer patient and a relative were recorded and analyzed by the Cancer Research Campaign Workshop Evaluation Manual . Patients ' and relatives ' anxiety were assessed with the State-Trait Anxiety Inventory-State . RESULTS No statistically significant change over time and between groups was observed . Mixed-effects modeling of changes in patients ' and relatives ' anxiety showed that decreases in both patients ' and relatives ' anxiety were linked with patients ' and relatives ' self-reported distress ( p = 0.031 and 0.005 ) , and that increases in both patients ' and relatives ' anxiety were linked with physicians ' breaking bad news ( p = 0.028 and 0.005 ) . CONCLUSION No impact of the training program was observed . Results indicate the need to further study communication skills which may help reduce patients ' and relatives ' anxiety especially when breaking bad news OBJECTIVES The quality of medical care by somatically treating physicians has considerable influence on the coping process in cancer patients . In outpatient psychosocial care , information supply and doctor-patient interaction are often considered difficult by the patients . This study therefore investigates the effects of a teaching and training programme on interactional skills of experienced physicians in dealing with cancer patients . METHODS In a pre-post comparison design , the effects of a 6-hour and a 24-hour interaction and teaching programme were compared . To measure the effects , interviews with st and ardised patients were carried out and analysed using the Medical Interaction Process System ( Ford 1998 ) . RESULTS About one third of all physicians practicing in the area of Mönchengladbach , Germany , could be motivated to participate in the programme . The physicians who received the 24-hour training showed a substantial improvement in interaction skills whereas no marked changes were seen in those physicians who had participated in the 6-hour training . CONCLUSIONS Interactional skills of experienced physicians can be improved by teaching and training programmes . Therefore , doctor-patient interaction training should be integrated into continuing medical education PURPOSE To measure the psychosocial attitudes and beliefs of physicians working within oncology in the United Kingdom and to examine whether beliefs alter after communication skills training . Additionally , to investigate whether physicians ' attitudes are reflected in communication behaviors with patients during interviews . METHODS Ninety-three physicians completed a 32-item Physician Psychosocial Belief ( PPSB ) question naire at baseline ( T1 ) before r and omization to attendance at a 3-day residential communication skills course ( n = 48 ) or a control group ( n = 45 ) . Three months later ( T2 ) , both groups completed another PPSB and a self- assessment question naire recording perceived changes in communication with patients . At both time points , physicians ' consultations with two consenting patients were videotaped . Communication behaviors were measured using the Medical Interaction Processing System . RESULTS Physicians who attended the course showed significantly improved attitudes and beliefs toward psychosocial issues compared with controls ( P = .002 ) . This improvement was reflected in the analysis of the videotaped recordings of their communication behaviors with patients . Expressions of empathy were more likely for the course group at T2 than the controls ( P = .02 ) , as were open questions ( P = .001 ) , appropriate responses to patient cues ( P = .005 ) , and psychosocial probing ( P = .041 ) . These objective findings were supported by physicians ' self report of changes in communication style during interviews with patients . CONCLUSION Our results show that a communication skills training intervention using behavioral , cognitive , and affective components not only increases potentially beneficial and more effective interviewing styles but can also alter attitudes and beliefs , thus increasing the likelihood that such skills will be used in the clinical setting PURPOSE Although there is wide recognition of the usefulness of improving physicians ' communication skills , no studies have yet assessed the efficacy of post-training consolidation workshops . This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program . METHODS Physicians , after attending the basic training program , were r and omly assigned to consolidation workshops or to a waiting list . Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group , and approximately 5 months after the end of basic training for the waiting-list group . Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual . Patients ' perceptions of communication skills improvement were assessed using a 14-item question naire . RESULTS Sixty-three physicians completed the training program . Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group . In simulated interviews , group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions ( P = .014 ) and utterances alerting patients to reality ( P = .049 ) , as well as a significant decrease in premature reassurance ( P = .042 ) . In actual patient interviews , results revealed a significant increase in acknowledgements ( P = .022 ) and empathic statements ( P = .009 ) , in educated guesses ( P = .041 ) , and in negotiations ( P = .008 ) . Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians ' underst and ing of their disease ( P = .004 ) . CONCLUSION Consolidation workshops further improve a communication skills training program 's efficacy and facilitate the transfer of acquired skills to clinical practice OBJECTIVE Recent studies have recognised that the communication skills learned in the training environment are not always transferred back into the clinical setting . This paper reports a study which investigated the potential of clinical supervision in enhancing the transfer process . METHODS A r and omised controlled trial was conducted involving 61 clinical nurse specialists . All attended a 3-day communication skills training workshop . Twenty-nine were then r and omised to 4 weeks of clinical supervision , aim ed at facilitating transfer of newly acquired skills into practice . Assessment s , using real and simulated patients , were carried out before the course , immediately after the supervision period and 3 months later . Interviews were rated objective ly using the Medical Interview Aural Rating Scale ( MIARS ) to assess nurses ' ability to use key skills , respond to patient cues and identify patient concerns . RESULTS Assessment s with simulated patients showed that the training programme was extremely effective in changing competence in all three key areas . However , only those who experienced supervision showed any evidence of transfer . Improvements were found in the supervised groups ' use of open questions , negotiation and psychological exploration . Whilst neither group facilitated more disclosure of cues or concerns , those in the experimental group responded more effectively to the cues disclosed , reduced their distancing behaviour and increasing their exploration of cues . CONCLUSIONS The study has shown that whilst training enhances skills , without intervention , it may have little effect on clinical practice . The potential role of clinical supervision as one way of enhancing the clinical effectiveness of communication skills training programmes has been demonstrated . PRACTISE IMPLICATION S : This study raises questions about the effectiveness of training programmes which do not incorporate a transfer element , and provides evidence to support the need for clinical supervision for clinical nurse specialist Purpose High- quality palliative care requires physicians who communicate effectively , yet many do not receive adequate training . Leading efforts to demonstrate the effectiveness of such training have involved time-intensive programs that included primarily attending physicians , which have been conducted outside of the United States . The goal was to evaluate the effect of a short course to improve residents ' communication skills delivering bad news and eliciting patients ' preferences for end-of-life care . Method This prospect i ve trial enrolled internal medicine residents at Duke University Medical Center from 1999 to 2001 . The course consisted of small-group teaching with lecture , discussion , and role-play . The outcome measure was observed communication skills delivering bad news and eliciting patients ' preferences for end-of-life treatment , assessed via audio-recorded st and ardized patient encounters before and after receiving the intervention . Results Thirty-seven residents received the intervention and 19 were in the control group . Residents attending the course demonstrated statistically significant increases in their overall skill ratings in the delivery of bad news , with improvement in the specific areas of information giving and responding to emotional cues . Although cumulative scores for discussion s about patient preferences for treatment did not increase , residents demonstrated enhanced specific skills including discussing probability , presenting clinical scenarios , and asking about prior experience with end-of-life decision making . Conclusion A relatively short , intensive course can improve the end-of-life communication skills of U.S. medical residents PURPOSE / OBJECTIVES To determine the effect of death education on attitudes and behavioral intentions of experienced nurses who care for hospitalized terminally ill adults and their families and to determine the influence of death education on nurses ' self-perceptions regarding supervision or peer review of their behavior toward dying patients and their families . DESIGN Experimental . SETTING Adult medical-surgical units in an urban teaching hospital . SAMPLE Self-selected sample ( n = 28 ) of registered nurses r and omly assigned into experimental ( n = 14 ) and control ( n = 14 ) groups . METHODS Both groups completed Waltman 's question naire Attitudes , Subjective Norms , and Behavioral intentions of Nurses Toward Care of Dying Patients and their Families , using a pretest/post-test format . The experimental group also received an educational intervention consisting of three two-hour didactic/experiential classes ; the control group received no intervention . MAIN RESEARCH VARIABLES Death education and nurses ' attitudes , subjective norms , and behavioral intentions toward care of dying patients and their families . FINDINGS The research er detected no significant difference in attitude between the two groups . The educational intervention had a significant positive effect on subjective norms . No significance was detected in overall analysis of behavioral intentions . CONCLUSIONS Death education had no effect on the attitudes or behavioral intentions of RNs toward care of dying patients and their families . The educational program did have a significant positive effect on nurses ' perceptions of how others might perceive their behavior toward dying patients and their families . IMPLICATION S FOR NURSING PRACTICE Death education for nurses , especially in areas of communication with patients and families , potentially may affect terminal care . The significant influence on subjective norms suggests a need to exp and death education to include all healthcare personnel PURPOSE This study aim ed to assess the impact on physicians ' detection of patients ' and relatives ' distress of six 3-h consolidation workshops ( CW ) following a 2.5-day communication skills basic training ( BT ) program and to investigate factors associated with detection of distress . METHODS Physicians , after BT , were r and omized to CW or to a waiting list . Physicians ' detection of patients ' and relatives ' distress was measured through differences between physicians ' ratings of patients ' and relatives ' distress ( VAS ) and patients ' and relatives ' self-reported distress ( HADS ) . Communication skills were analysed according to the CRCWEM . RESULTS Mixed-effects modelling of physicians ' detection of patients ' distress showed a positive group by time effect in favour of physicians in the CW group . Detection of patients ' distress was associated negatively with patients ' distress , positively with physicians ' concurrent use of psychological assessment and supportive skills , and negatively with general assessment skills . Mixed-effects modelling of physicians ' detection of relatives ' distress showed no significant group by time effect . Detection of relatives ' distress was associated negatively with relatives ' distress and with general assessment skills . CONCLUSION CW following a 2.5-day BT are needed to improve physicians ' detection of patients ' distress in three-person interviews . Results indicate the need to further improve physicians ' detection of relatives ' distress BACKGROUND Although patients with cancer are often accompanied by a relative during medical interviews , to the authors ' knowledge little is known regarding the efficacy of communication skills training programs on physicians ' communication skills in this context . The objective of the current study was to assess the efficacy of 6 consolidation workshops , 3 hours in length , that were conducted after a 2.5-day basic training program . METHODS After attending the basic training program , physicians were assigned r and omly to consolidation workshops or to a waiting list . Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline , after consolidation workshops for the consolidation-workshops group , and 5 months after the end of basic training for the waiting-list group . Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual . Patients ' and relatives ' perceptions of and satisfaction with physicians ' communication performance were assessed using a 15-item question naire . RESULTS Sixty-two physicians completed the training program . Compared with physicians who participated to the basic training program , when addressing the patient , physicians who were r and omized to the consolidation workshops used more open , open directive , and screening questions ( P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews ) and elicited and clarified psychologic concerns more often ( P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews ) . When they addressed the relative , physicians who were r and omized to the consolidation workshops gave less premature information ( P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews ) . When they addressed the patient and the relative simultaneously , physicians who were r and omized to the consolidation workshops used more empathy , educated guesses , alerting to reality , confronting , negotiating , and summarizing ( P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews ) . Patients , but not relatives , who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews ( P = 0.022 ) . CONCLUSIONS Six 3-hour consolidation workshops result ed in improved communication skills addressed to patients and to relatives . The current results showed that the transfer of skills addressing relatives ' concerns remained limited and that consolidation workshops should focus even more systematic ally on the practice of three-person interviews PURPOSE Psychological morbidity in cancer patients is common , but often undetected and untreated . We developed a communication skills training ( CST ) program targeting this issue , and evaluated its impact on doctor behaviour . PATIENTS AND METHODS Thirty of 35 oncologists from six teaching hospitals in six Australian cities , participated . The CST was a 1.5-day intensive face-to-face workshop incorporating presentation of principles , a DVD modelling ideal behaviour and role-play practice , followed by four 1.5 h monthly video-conferences incorporating role-play of doctor-generated scenarios . Doctors were r and omized to receive the CST or not . Simulated patient interviews were videotaped and coded at baseline , after CST and 6 months later . Doctors completed question naires assessing stress and burnout at the same time points . RESULTS Doctors in the intervention group displayed more creating environment and fewer blocking behaviours at both follow-ups ; however , these differences did not reach statistical significance . Intervention doctors valued the training highly , but did not report substantial reductions in stress and burnout . CONCLUSIONS This short training programme demonstrated a positive effect on aspects of doctor behaviour . Video-conferencing after a short training course may be an effective strategy for delivering CST The usefulness of psychological training programs ( P.T.P. ) in health care setting s devoted to cancer care is beginning to be recognised but their content , form and effectiveness need further investigation . Seventy-two oncology nurses were r and omly assigned to a 24-h P.T.P. or to a waiting list period . Attitudes were assessed by a semantic differential question naire , occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by st and ardised videotaped role-playing exercises . These were used to compare trained ( T.S. ) and control subjects ( C.S. ) . The results show a significant training effect on attitudes ( P = 0.05 ) , especially on those related to self concept ( P = 0.004 ) , and on the level of occupational stress related to inadequate preparation ( P = 0.02 ) . Limited changes were found regarding post-training communication skills . T.S. were significantly more in control of the interview than C.S. ( P = 0.02 ) . The results indicate that 24-h P.T.P. assessed here are effective . The data also demonstrate the need to consoli date the skills acquired by regular post-training sessions |
478 | 12,918,009 | Results showed a statistically significant reduction in joint tenderness , but no clinical benefit from C-TENS over placebo in relief of joint tenderness .
REVIEW ER 'S CONCLUSIONS There are conflicting effects of TENS on pain outcomes in patients with RA .
AL-TENS is beneficial for reducing pain intensity and improving muscle power scores over placebo while , conversely , C-TENS result ed in no clinical benefit on pain intensity compared with placebo .
However C-TENS result ed in a clinical benefit on patient assessment of change in disease over AL-TENS .
More well design ed studies with a st and ardized protocol and adequate number of subjects are needed to fully conclude the effect of C-TENS and AL-TENS in the treatment of RA of the h and | BACKGROUND Rheumatoid arthritis ( RA ) is a chronic , inflammatory , system disease .
It commonly affects the small peripheral joints ( such as fingers and wrist ) .
The main goals of intervention for RA are preventing joint deformity , preserving joint function , and reducing inflammation and pain .
Transelectrical nerve stimulation ( TENS ) is a form of electrotherapy and is thought to produce analgesia according to the gate control theory .
OBJECTIVES To determine the efficacy and safety of TENS in the treatment of RA of the h and .
The primary outcomes of interest were relief of grip pain and resting pain intensity , relief of joint tenderness , number of tender joints and patient assessment of disease .
The secondary objective was to determine the most effective mode of TENS application in pain control . | A prospect i ve study of the use of transcutaneous neural stimulation ( TNS ) in 90 arthroscopic knee surgery pa tients was performed to determine : ( 1 ) if TNS is as effective as traditional pain medication in treating post operative knee pain ; and ( 2 ) if patients that had received TNS regain preoperative motion and strength quicker than the control population . The patients were divided into three equal groups . Group I consisted of patients with no TNS unit , Group II had a " placebo " unit , and Group III had a " live " unit . Preoperatively , each patient received an isokinetic muscle examination , orientation to the TNS unit , leg circumference measurements , and exercise instruction . An isokinetic muscle examination and leg circumference measurements were repeated at 1 , 3 , and 7 weeks postoperatively . Additionally , the amount of pain and medication required was analyzed . The results of the study indicated that the use of a TNS unit is an effective adjunct in decreasing postoperative pain in 93 % of patients . The amount of pain and total pain medication required was greatest in the control group , less in the placebo , and markedly reduced in the TNS group . A comparison among the three groups revealed that the TNS group regained the following preoperative values 1 month sooner than the other two groups ( 3 as opposed to seven weeks postoperatively ) : isokinetic power in flexion and extension ( P < 0.05 ) , range of motion ( P < 0.02 ) , and leg volume ( P < 0.05 ) . There was no correlation between the pain and irregular wave forms on the isokinetic graph . The only compli cation noted was skin irritation at the electrode sites . TNS has been shown to be a significant benefit in the treatment of postoperative knee pain and in hastening recovery of muscular function through a full range of motion Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment treatment was withdrawn . Each subject experienced in some order three 3-week treatment phases : NSAID plus placebo TENS ; TENS plus placebo drug ; and double placebo . A broad range of pain measures was used , including daily diary ratings , and four-times-per-day ratings entered into a small electronic data logger ( the PIPER ) worn by the subject . A substantial placebo response occurred across all conditions , which may have masked treatment differences . Broad comparisons across subjects , combining the four main measures of pain , found no significant differences among the three experimental treatments . Analysis of diary and PIPER data for individuals suggested that , in a small minority of subjects , the NSAID plus placebo TENS combination may be more effective than double placebo . The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures , suggesting the value of very frequent pain assessment s , such as those entered by a subject into the PIPER , in the study of chronic pain Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor This r and omized study analyzed the effectiveness of postoperative transcutaneous electrical nerve stimulation ( TENS ) used continuously for the first three postoperative days following total knee replacement ( TKR ) for 1 ) pain relief , 2 ) knee flexion arc , 3 ) narcotic dosage , and 4 ) hospital stay . Group 1 ( N = 18 ) received sensory threshold TENS and group 2 ( N = 18 ) received subthreshold TENS . Both groups also used continuous passive motion during their hospitalization as did patients from group 3 ( control , N = 12 ) that did not receive TENS . Pain decrease from postoperative day 1 - 3 was 50 % for group 1 patients and 38 % for group 2 patients , as measured by the visual analog scale . Wilcoxon Rank Sum did not show a significant difference ( p > 0.05 ) for pain relief or hospital stay for these two groups . Analysis of variance failed to show significant differences ( p > 0.05 ) for knee flexion arc or narcotic dosage for the three groups . Although not statistically significant , an observed decrease in pain may be the only indication for postoperative TENS after TKR . J Orthop Sports Phys Ther 1990;11(12):599 - 604 Summary The analgesic effects of high frequency transcutaneous electrical nerve stimulation ( TNS ) , “ acupuncture-like ” TNS and placebo TNS were evaluated in 33 patients with rheumatoid arthritis and chronic h and pain using a r and omized , double-blind , non-crossover design . An oscilloscope was employed to monitor the stimulator output in the TNS treatment groups and to provide strong suggestion and a focus of attention in the placebo treatment group . The two forms of TNS were applied at the highest intensity that could be tolerated by patients . Assessment s of resting pain , joint tenderness , grip strength and grip pain were made before and after treatment . The pain and joint tenderness measurements showed high frequency TNS , “ acupuncture-like ” TNS and placebo TNS to be equally effective in producing analgesia of similar degree and trend over time . The grip strength measurements showed no significant change . The results obtained with placebo are probably due to the suggestion and attention effects of the visual stimulus . The implication s of these results in respect to pain control pathways are discussed . Although TNS given at high intensity was shown to be no better than placebo applied with strong suggestion , this does not preclude its use as a method of pain control in rheumatoid arthritis The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a r and omised , double-blind , non-crossover study lasting three weeks . Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated . Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping . In addition , grip strength , measured as power and work done , immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessment s. No significant improvement was shown for the placebo group The effect of transcutaneous nerve stimulation ( TNS ) on joint pain was studied in patients with rheumatoid arthritis . Three different forms of TNS were used in an attempt to evaluate the influence of placebo effects . The results were evaluated by means of loading tests and from the patients ' own assessment s of pain relief . High intensity TNS near the painful joint gave pain relief of varying degree in 95 % of the patients , while TNS of low intensity and TNS applied at a remote site gave an improvement in 75 % and 5 % respectively . It seems quite clear that TNS is effective in reducing joint pain . There are a number of factors which intimate that this improvement is not merely a placebo effect The effect of transcutaneous nerve stimulation ( TNS ) was evaluated and compared with placebo TNS in 19 patients ( 17 women , mean age 33 years ) with orofacial functional pain and rheumatic disease involving the temporom and ibular joint . In two double-blind noncrossover experiments , high frequency TNS ( 100 Hz ) and low frequency TNS ( 2 Hz ) were evaluated by comparison of the patients ' functional and rest pain , muscle and joint tenderness , and jaw function . A significant treatment effect was obtained for all treatment methods regarding functional and rest pain and muscle and joint tenderness . None of the parameters except functional pain , which improved significantly more after high frequency TNS than placebo TNS , revealed any difference between the methods . Jaw function , however , revealed a few differences between high frequency TNS and placebo TNS |
479 | 28,455,366 | Beneficial effects were also seen for symptoms .
Conclusions The results of this review suggest beneficial effects of exercises on inflammation , joint damage and symptoms in patients with IRDs | Objective To investigate the effects of cardiorespiratory and strength exercises on disease activity for patients with inflammatory rheumatic diseases ( IRDs ) . | The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity . Maximal O2 uptake increased significantly , whereas heart rate at stage 2 and rate of perceived exertion decreased significantly , in the training group compared with the controls . Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training . Training did not induce changes in blood mononuclear cell sub population s , proliferative response , or natural killer cell activity . Furthermore the plasma concentrations of interleukin-1 alpha , interleukin-1 beta , and interleukin-6 did not change in response to training . It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis Objective . To evaluate the outcome of resistive home exercise and its possible longterm influence on health , disability , and disease activity in patients with active polymyositis ( PM ) or dermatomyositis ( DM ) . Methods . Nineteen patients with recent-onset PM/DM were included after introduction of high-dose prednisolone . They were assessed by independent assessors as to perceived health , muscle performance , aerobic capacity , and serum creatine phosphokinase ( CPK ) at baseline and after 24 weeks , including repeated muscle biopsies at 24 weeks ( single-blinded r and omized controlled study ) , and in an open-label followup at 52 , 78 , and 104 weeks . Patients were r and omized to 12 weeks , 5 days/week resistive home exercise with telephone support and encouragement for another 12 weeks of twice-a-week home or gym exercise ( EG , n = 10 ) or to 24 weeks , 5 days/week range of motion exercise ( CG , n = 9 ) . Patients in the CG group without inflammatory infiltrates in muscle biopsies at 24 weeks were invited to the 12-week resistive home exercises . Results . At baseline , the EG had poorer perceived health , but otherwise the groups were comparable . At 24 weeks , both groups improved in muscle performance and aerobic capacity ( p < 0.001 to < 0.05 ) with no signs of increased inflammation assessed by CPK levels or muscle biopsies . Both groups improved in muscle performance and aerobic capacity up to 52 weeks ( p < 0.05 ) lasting to 104 weeks in the EG ( p < 0.05 ) and presented minor improvements in perceived health . Conclusion . Our study supports the safety of resistive exercise in patients with active PM/DM but did not reveal any between-group differences in exercise effects . An individually adapted physical therapist – supervised home exercise program might be recommended in early active PM/DM , with regular evaluation of muscle performance and health OBJECTIVE To evaluate the effects of a 12 month , weight bearing , aerobic exercise program on disease activity , physical function , and bone mineral density ( BMD ) in women with rheumatoid arthritis ( RA ) taking low dose prednisone . METHODS A group of women with RA ( n = 23 ) not receiving steroid therapy and in American College of Rheumatology functional class I or II was compared to 30 steroid treated patients with similar demographics . The latter group was r and omized to usual care ( n = 16 ) or an aerobic , weight bearing exercise program ( n = 14 ) 3 times a week for 12 months . All subjects were recruited from an outpatient rheumatology clinic or physical therapy department and met the study inclusion criteria . Outcome measures included disease activity ( erythrocyte sedimentation rate , active joint count ) , physical function ( Health Assessment Question naire disability index , activity level ) and BMD of the spine and femoral neck ( by dual energy projection radiology ) . RESULTS Subjects in the exercise group had a small but nonsignificant decrease in disease activity and statistically significant improvements in function ( p = 0.05 ) and activity levels ( p = 0.05 ) . BMD remained unchanged in the exercise group , decreased significantly ( p = 0.004 ) in the nonsteroid comparison group ( hip ) , and changed nonsignificantly in the control group . However , between-group changes in spinal BMD of the steroid treated groups was not significant ( p = 0.09 ) . CONCLUSION Women with RA taking low dose steroid therapy can safely participate in a dynamic , weight bearing exercise program with positive effects on their physical function , activity and fitness levels , and BMD with no exacerbation of disease activity OBJECTIVE To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the h and s and feet in patients with rheumatoid arthritis ( RA ) . METHODS Data of the 281 completers of a 2 year r and omised controlled trial comparing the effects of usual care physical therapy ( UC ) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage ( Larsen score ) of the h and s and feet . Potential determinants of outcome were defined : disease activity , use of drugs , change in physical capacity and in bone mineral density , and attendance rate at exercise sessions . RESULTS After 2 years , the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC . The mean ( SD ) increase in damage was 3.5 ( 7.9 ) in the exercise group and 5.7 ( 10.2 ) in the UC group , p = 0.045 . Separate analysis of the damage to the h and s and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the h and s. The rate of damage was independently associated with less disease activity , less frequent use of glucocorticoids , and with an improvement in aerobic fitness . CONCLUSION The progression of radiological joint damage of the h and s and feet in patients with RA is not increased by long term high intensity weightbearing exercises . These exercises may have a protective effect on the joints of the feet Objective . Sleep disturbance and chronic fatigue are common in rheumatoid arthritis ( RA ) and contribute to disability , symptomatology , and healthcare use . It has long been recognized in other population s that exercise can improve sleep and diminish fatigue . The effect of exercise on sleep quality and fatigue in RA has not been evaluated . Methods . Ours is a r and omized controlled study in RA to determine the effect of an exercise program on sleep quality and fatigue . These were measured using the Pittsburgh Sleep Quality Index and the Fatigue Severity Scale . Patients were r and omized to either a 12-week , home-based exercise intervention or usual care . The exercise program consisted of specific exercises to target individual deficiencies identified using the Health Assessment Question naire ( HAQ ) with cardiovascular work as per the guidelines . The intervention group was evaluated on a 3-week basis . Full evaluation was carried out at baseline and at 12 weeks . Results . Forty patients were r and omized to the intervention with 38 controls . In the exercise intervention group , there was a statistically significant improvement in HAQ ( p = 0.00 ) , pain ( p = 0.05 ) , stiffness ( p = 0.05 ) , sleep quality ( p = 0.04 ) , and fatigue ( p = 0.04 ) . In our control group , there was a statistically significant improvement demonstrated in their overall perceptions of the benefits of exercise , but none of the other variables . Conclusion . Our study demonstrates that an exercise program result ed in significant improvement in sleep quality and fatigue . This is particularly interesting given the importance of fatigue as an outcome measure in RA and gives us yet another reason to prescribe exercise in this population AIM The aim of the study was to compare the effects of conventional exercise ( CE ) , swimming and walking on the pulmonary functions , aerobic capacity , quality of life , Bath indexes and psychological symptoms in patients with ankylosing spondylitis ( AS ) . METHODS Forty-five patients were r and omised into either swimming ( group 1 ) , walking ( group 2 ) , CE group ( group 3 ) . Patients in Group 1 performed CE and swimming , patients in Group 2 performed CE and walking and patients in Group 3 performed CE only . Exercise sessions were performed three times a week for a period of six weeks . Patients were assessed before and after the rehabilitation program , with respect to , pulmonary function test ( forced vital capacity [ FVC , mL ] , forced expiration volume in one second [ FEV1 , mL ] , FEV1/FVC ( % ) and vital capacity [ VC , mL ] ) , maximal oxygen uptake ( pV.O2 ) , 6-minute walking test ( 6MWT ) , Bath Ankylosing Spondylitis Functional Index , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Metrology Index , Nottingham Health Profile and Beck Depression Inventory . RESULTS There were significant increases in pVO2 and 6MWT after treatment in Groups 1 and 2 ( P<0.05 ) . FeV1 , FVC and VC improved significantly with treatment in all three groups ( P<0.05 ) . A statistically significant improvement was observed in energy , emotional reaction and physical mobility sub-scores of NHP in three exercise groups after completion of the exercise program ( P<0.05 ) . CONCLUSIONS Swimming , walking and CE had beneficial effects on the quality of life and pulmonary functions . Aerobic exercises such as swimming and walking in addition to CE increased functional capacities of patients Background Physical therapy is recommended for the management of axial spondyloarthritis ( axSpA ) and flexibility exercises have traditionally been the main focus . Cardiovascular ( CV ) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases . Therefore , the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. Methods In a single blinded r and omized controlled pilot study the exercise group ( EG ) performed 12 weeks of endurance and strength exercise while the control group ( CG ) received treatment as usual . The primary outcome was the Ankylosing Spondylitis ( AS ) Disease Activity Score ( ASDAS ) . Secondary outcomes included patient reported disease activity ( Bath AS Disease Activity Index [ BASDAI ] ) , physical function ( Bath AS Functional Index [ BASFI ] ) , and CV risk factors measured by arterial stiffness ( Augmentation Index [ Alx ] ) and Pulse Wave Velocity [ PWV ] ) , cardiorespiratory fitness ( VO2 peak ) and body composition . ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences , and Mann Whitney U-test was used for outcomes with skewed residuals . Results Twenty-eight patients were included and 24 ( EG , n = 10 , CG , n = 14 ) completed the study . A mean treatment effect of −0.7 ( 95%CI : −1.4 , 0.1 ) was seen in ASDAS score . Treatment effects were also observed in secondary outcomes ( mean group difference [ 95%CI ] ) : BASDAI : −2.0 ( −3.6 , −0.4 ) , BASFI : −1.4 ( −2.6 , −0.3 ) , arterial stiffness ( estimated median group differences [ 95 % CI ] ) : AIx ( % ) : −5.3 ( −11.0 , −0.5 ) , and for PVW ( m/s ) : −0.3 ( −0.7 , 0.0 ) , VO2 peak ( ml/kg/min ) ( mean group difference [ 95%CI ] : 3.7 ( 2.1 , 5.2 ) and trunk fat ( % ) : −1.8 ( −3.0 , −0.6 ) . No adverse events occurred . Conclusion High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial . Trial Registration Clinical Trials.gov The objective was to study the long-term effect ( 2 years ) of different training programs in patients with rheumatoid arthritis . The method was a r and omized trial with 75 patients participating . The measured variables included morning stiffness , a pain score , number of swollen joints , a health assessment score , a functional score , ESR , Hb , the cost of medicine , and progression using X-rays of h and s and feet . The results showed no effect of training on the disease activity or on the progression of the disease . The conclusion is that although most patients are in favour of training , the present study does not support that training lessons per se affect the disease activity or the progression of the disease OBJECTIVE The benefit of long-term physical training in patients with chronic polymyositis or dermatomyositis ( PM/DM ) was studied prospect ively . METHODS Eight patients with chronic PM/DM participated in a training programme for 6 months . A group of five PM/DM patients without any physical training was observed for control purpose s. RESULTS While there was no significant change in serum creatine phosphokinase ( CPK ) levels , the ' activities of daily living ( ADL ) ' score improved significantly ( P < 0.03 ) , peak isometric torque ( PIT ) generated by muscle groups in the lower extremities rose significantly ( P < 0.03 ) and there was a statistically highly significant increase in peak oxygen uptake ( VO2max ) relative to body weight ( P < 0.02 ) due to the long-term training . The patients improved their aerobic capacity by 28 % , which is clinical ly significant . In the untrained patients , no improvement in these target parameters was observed . CONCLUSION In clinical ly stable DM/PM patients , long-term physical training can safely be performed and is recommended as part of a comprehensive rehabilitation management , particularly in view of the cardiopulmonary risk in these patients OBJECTIVE To evaluate the impact of a 2-year program of strength training on muscle strength , bone mineral density ( BMD ) , physical function , joint damage , and disease activity in patients with recent-onset ( < 2 years ) rheumatoid arthritis ( RA ) . METHODS In this prospect i ve trial , 70 RA patients were r and omly assigned to perform either strength training ( all major muscle groups of the lower and upper extremities and trunk , with loads of 50 - 70 % of repetition maximum ) or range of motion exercises ( without resistance ) twice a week ; all were encouraged to engage in recreational activities 2 - 3 times a week . All patients completed training diaries ( evaluated bi-monthly ) and were examined at 6-month intervals . All were treated with medications to achieve disease remission . Maximum strength of the knee extensors , trunk flexors and extensors , and grip strength was measured with dynamometers . BMD was measured at the femoral neck and lumbar spine by dual x-ray densitometry . Disease activity was determined by the Disease Activity Score , the extent of joint damage by the Larsen score , and functional capacity by the Health Assessment Question naire ( HAQ ) ; walking speed was also measured . RESULTS Sixty-two patients ( 31 per group ) completed the study . Strength training compliance averaged 1.4 - 1.5 times/week . The maximum strength of all muscle groups examined increased significantly ( 19 - 59 % ) in the strength-training group , with statistically significant improvements in clinical disease activity parameters , HAQ scores , and walking speed . While muscle strength , disease activity parameters , and physical function also improved significantly in the control group , the changes were not as great as those in the strength-training group . BMD in the femoral neck and spine increased by a mean + /- SD of 0.51 + /- 1.64 % and by 1.17 + /- 5.34 % , respectively , in the strength-training group , but decreased by 0.70 + /- 2.25 % and 0.91 + /- 4.07 % in the controls . Femoral neck BMD in the 17 patients with high initial disease activity ( and subsequent use of oral glucocorticoids ) remained constantly at a statistically significantly lower level than that in the other 45 patients . CONCLUSION Regular dynamic strength training combined with endurance-type physical activities improves muscle strength and physical function , but not BMD , in patients with early RA , without detrimental effects on disease activity Thirty-nine consecutive patients with recent-onset rheumatoid or psoriatic arthritis were r and omly allotted for six months period either to the experimental progressive dynamic strength training group ( EG , 10 women and 11 men ; 41 + /- 10 yrs ) , or to the control group ( CG , 10 women and 8 men ; 45 + /- 11 yrs ) who just maintained their habitual physical activities . All patients received antirheumatic medication throughout the experimental period . During the study period significant improvements took place in the EG in maximal muscle strength of all examined muscle groups ( 31.5 % for the knee extensors , p < 0.001 ; 14.8 % and 10.7 % for the trunk flexors and extensors , p < 0.01 ; 27.8 % and 20.4 % for grip strength , p < 0.001 ) as well as in erytrocyte sedimentation rate ( p < 0.05 ) . Ritchie 's articular index ( RI ) ( p < 0.001 ) and HAQ ( p < 0.01 ) . In the CG only the decrease in RI was statistically significant ( p < 0.05 ) . Erosive changes in joints increased only slightly and less in the EG than in the CG . The present results suggest that dynamic strength training in early arthritis increases the neuromuscular performance without detrimental effects on disease activity or joint damage Objective Patients with rheumatoid arthritis ( RA ) are characterized by reduced physical activity and increased morbidity and mortality from cardiovascular disease ( CVD ) . The aim of this study was to investigate associations between levels of physical activity and CVD risk profile in RA patients . Methods Levels of physical activity were assessed in 65 RA patients ( 43 females ) . Using the International Physical Activity Question naire , patients were allocated into three groups : active , moderately active and inactive . Anthropometric characteristics , RA activity/severity , multiple classical and novel CVD risk factors and 10-year CVD event probability were assessed and compared among the three groups . Results Significant differences were detected among groups in systolic blood pressure ( P = 0.006 ) , cholesterol ( P < 0.001 ) , low-density lipoprotein ( P = 0.01 ) , homeostasis model assessment ( P = 0.001 ) , type-1 plasminogen activator inhibitor antigen ( P < 0.001 ) , tissue-type plasminogen activator antigen ( P = 0.019 ) , homocysteine ( P = 0.027 ) , fibrinogen ( P = 0.001 ) , apolipoprotein B ( P = 0.002 ) and von Willebr and Factor ( P = 0.001 ) , with a consistent deterioration from the physically active to the physically inactive group . Multivariate analysis of variance revealed that levels of physical activity were significantly associated with the differences in all of the above variables ( P < 0.05 ) after adjustment for age , weight , sex , smoking status , as well as RA disease activity and severity . Conclusion This cross-sectional study suggests that physically inactive RA patients have significantly worse CVD risk profile compared with physically active patients . The possible beneficial impact of increased physical activity , including structured exercise , to the CVD risk of RA patients needs to be accurately assessed in prospect i ve studies . Eur J Cardiovasc Prev Rehabil 16:188 - 194 © 2009 The European Society of The effectiveness of an exercise prescription and unsupervised home exercise programme was tested on 37 subjects with rheumatoid arthritis and 34 with systemic lupus erythematosus . Subjects were r and omly assigned to control or stationary bicycling at home , using loaned bicycles . Exercise subjects ( with bicycles ) did better than controls , but not significantly , on all outcome d measures ( exercise tolerance test , fatigue , depression and helplessness ) at 3 months . Bicycles were recl aim ed at 3 months and all subjects in both groups given instructions for home exercise . Exercise in the second 3 months was predicted primarily by baseline exercise habits and fatigue . It is concluded that although safe , unsupervised home exercise programmes may benefit few patients . Future research should address methods of stimulating and maintaining unsupervised exercise programmes in patients with systemic rheumatic disease OBJECTIVE To determine the effect of a low load resistance exercise training program on muscle strength , functional outcome , and cardiovascular endurance . METHODS Forty-nine patients , 37 women and 12 men between the ages of 35 - 76 yrs ( mean 60.5 yrs ) , with definite rheumatoid arthritis ( RA ) functional class II and III ( mean disease duration of 10.5 yrs ) were r and omly assigned to exercise and control groups for a 12 wk resistive muscle training program . A circuit weight bearing form of training was incorporated using light loads with high repetitions . A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation . Baseline and post-intervention evaluations included joint activity , muscle strength , endurance , functional outcome , and self-report . Cardiovascular fitness measured by treadmill time , anaerobic threshold and peak oxygen consumption ( VO2 ) in this group were assessed at baseline and 12 wks . RESULTS A significant improvement at 12 wks was noted in the exercise group for self-reported joint count ( p = 0.02 ) , number of painful joints ( p = 0.004 ) , HAQ ( p = 0.012 ) , sit-to-st and time ( p = 0.02 ) , grip strength ( p = 0.05 ) knee extension 60 degrees ( p = 0.03 ) , Arthritis Impact Measurement Scales dexterity ( p = 0.02 ) , and time to anaerobic threshold ( p = 0.03 ) . Significant improvement in the exercise group compared to the control group was noted for self-reported joint count ( p = 0.02 ) , night time pain ( p = 0.05 ) , and sit-to-st and time ( p = 0.02 ) . Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption ( VO2 ) noted . Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients . They were excluded from the study and subsequent workup revealed significant coronary artery disease . CONCLUSION Low load resistive muscle training increased functional capacity as reported by patients and is a clinical ly safe form of exercise in functional class II and III RA . Screening this population for dormant coronary artery disease is recommended OBJECTIVE : To investigate the benefit of intensive dynamic exercises in comparison to range of motion ( ROM ) and isometric exercises in rheumatoid arthritis . METHODS : 100 consecutive rheumatoid arthritis patients on stable medication were r and omly assigned to ( 1 ) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at 70 - 85 % of the age predicted maximum heart rate , ( 2 ) range of motion ( ROM ) exercises and isometric exercises in a group , ( 3 ) individual isometric and ROM exercises , and ( 4 ) home instructions for isometric and ROM exercises . Variables of physical condition , muscle strength , joint mobility , daily functioning ( HAQ ) , and disease activity were assessed before and after the 12 week exercise course , and 12 weeks thereafter . An intention to treat analysis was performed . RESULTS : Increases in aerobic capacity ( n = 77 ) , muscle strength , and joint mobility in the high intensity exercise programme were respectively 17 % , 17 % and 16 % and differed significantly from the changes in aerobic capacity , muscle strength , and joint mobility in the other exercise groups . No deterioration of disease activity was observed . Twelve weeks after discontinuation of the exercise course the gain in physical capacity had disappeared . CONCLUSIONS : Intensive dynamic training is more effective in increasing aerobic capacity , joint mobility , and muscle strength than ROM exercises and isometric training in rheumatoid arthritis patients with well controlled disease OBJECTIVE To confirm , in a r and omized controlled trial ( RCT ) , the efficacy of high-intensity progressive resistance training ( PRT ) in restoring muscle mass and function in patients with rheumatoid arthritis ( RA ) . Additionally , to investigate the role of the insulin-like growth factor ( IGF ) system in exercise-induced muscle hypertrophy in the context of RA . METHODS Twenty-eight patients with established , controlled RA were r and omized to either 24 weeks of twice-weekly PRT ( n = 13 ) or a range of movement home exercise control group ( n = 15 ) . Dual x-ray absorptiometry-assessed body composition ( including lean body mass [ LBM ] , appendicular lean mass [ ALM ] , and fat mass ) ; objective physical function ; disease activity ; and muscle IGFs were assessed at weeks 0 and 24 . RESULTS Analyses of variance revealed that PRT increased LBM and ALM ( P < 0.01 ) ; reduced trunk fat mass by 2.5 kg ( not significant ) ; and improved training-specific strength by 119 % , chair st and s by 30 % , knee extensor strength by 25 % , arm curls by 23 % , and walk time by 17 % ( for objective function tests , P values ranged from 0.027 to 0.001 versus controls ) . In contrast , body composition and physical function remained unchanged in control patients . Changes in LBM and regional lean mass were associated with changes in objective function ( P values ranged from 0.126 to < 0.0001 ) . Coinciding with muscle hypertrophy , previously diminished muscle levels of IGF-1 and IGF binding protein 3 both increased following PRT ( P < 0.05 ) . CONCLUSION In an RCT , 24 weeks of PRT proved safe and effective in restoring lean mass and function in patients with RA . Muscle hypertrophy coincided with significant elevations of attenuated muscle IGF levels , revealing a possible contributory mechanism for rheumatoid cachexia . PRT should feature in disease management OBJECTIVE To test the efficacy of a grade d aerobic exercise programme in treating fatigue in systemic lupus erythematosus . METHODS Ninety-three patients with systemic lupus erythematosus without active disease in any major organ were r and omized , using a minimization protocol , to 12 weeks of grade d exercise therapy , relaxation therapy or no intervention . RESULTS Analysis by intention to treat showed that 16 of the 33 ( 49 % ) patients in the exercise group rated themselves as ' much ' or ' very much ' better compared with eight out of 29 ( 28 % ) in the relaxation group and five out of 32 ( 16 % ) in the control group ( chi2=8.3 , df=2 , P=0.02 ) . Fatigue improved significantly on one out of three measures after exercise therapy and there was a trend for fatigue to improve on all measures after exercise . CONCLUSION These findings support the use of appropriately prescribed grade d aerobic exercise in the management of patients with fatigue and systemic lupus erythematosus Objective . To evaluate the effects of aerobic exercise in patients with ankylosing spondylitis ( AS ) . Methods . Seventy patients classified with AS by the modified New York criteria were included . The patients were r and omly assigned into 2 groups . The intervention group ( IG ) performed 50 min of walking followed by stretching exercises 3 times a week for 12 weeks . The control group ( CG ) performed only stretching exercises . The outcome measurements were the Bath indexes [ Bath AS Functional Index ( BASFI ) , Bath AS Disease Activity Index ( BASDAI ) , and Bath AS Metrology Index ( BASMI ) ] , Health Assessment Question naire for the Spondyloarthropathies ( HAQ-S ) , AS Disease Activity Score ( ASDAS ) , the 6-min walk test ( 6MWT ) , chest expansion , and the Medical Outcomes Study Short Form-36 . Aerobic capacity was assessed by ergospirometry on a treadmill . Routine laboratory techniques were used in determining lipid levels . Assessment s were performed immediately before r and omization and after 6 , 12 , and 24 weeks . Results . Thirty-five patients were r and omized to the IG and 35 to the CG . There was significant improvement in the BASFI , HAQ-S , BASMI , BASDAI , and ASDAS in both groups ( p < 0.05 ) , but did not differ between groups . There was a significant increase in the walking distance in the 6MWT in the IG compared with CG ( p < 0.001 ) . The IG showed significant improvement in cardiopulmonary capacity compared with CG . Cholesterol and triglyceride levels did not change in either group . Conclusion . In patients with AS , aerobic training improved walking distance and aerobic capacity . Aerobic training did not provide additional benefits in functional capacity , mobility , disease activity , quality of life , and lipid levels when compared with stretching exercises alone Objective : To assess the effects of a 16-week progressive , individualized , high-intensity strength training program on muscle strength , pain , and function in patients with rheumatoid arthritis ( RA ) . Methods : Twenty-four RA patients ( men , n = 5 ; women , n = 19 ) receiving infliximab participated in a r and omized controlled trial . The strength training ( ST ) group ( n = 16 ) participated in a supervised program 3 times per week , and the control ( C ) group ( n = 8) continued with st and ard of care as overseen by their rheumatologist . Assessment s were completed at baseline and at weeks 8 and 16 . Strength was measured by 3 repetition maximum ( 3RM ) , isometric h and dynamometer , and isokinetic dynamometer . A 100-mm visual analogue scale was used to assess pain . Functional performance was derived from a timed 50-foot walk and the Health Assessment Question naire Disability Index . Results : The mean percent increase in strength ( 3RM ) for the ST group from baseline to week 16 was 46.1 % ± 31.6 % ( P < 0.01 ) ( mean of all three 3RM exercises : hammer curl , leg press , and incline dumbbell press ) , with mean gains in strength up to 4 times that of baseline values reported in all strength training exercises ( upper and lower body ) performed during exercise sessions . On average , right-h and grip strength increased by 2.9 ± 4.0 kg in the ST group , in comparison with a loss of 1.2 ± 3.0 kg in the C group over 16 weeks . The ST group had a 53 % reduction in pain , in comparison with almost no change in the C group . The ST group had a significant improvement in 50-foot walk time , with a mean reduction of −1.2 ± 1.6 seconds , in comparison with the C group ( mean increase of 0.8 ± 1.0 seconds ; P = 0.01 ) over the 16 weeks . There was a clinical ly important difference ( predefined as mean change ±0.25 ) in the Health Assessment Question naire Disability Index in the ST group ( −0.4 ± 0.4 ) but not in the C group ( −0.1 ± 0.4 ) . Conclusion : High-intensity strength training in RA patients with varying levels of disease activity and joint damage had a large , significant effect on strength , and led to improvements in pain and function , with additive patient benefits beyond the effect of their infliximab use To determine the effects of a 12‐week endurance exercise program on health , disability , VO2 max , and disease activity in a multicenter r and omized controlled trial in patients with established polymyositis ( PM ) and dermatomyositis ( DM ) , and to evaluate health and disability in a 1‐year open extension study OBJECTIVE There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis ( RA ) . We undertook this r and omized , controlled , multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program ( Rheumatoid Arthritis Patients In Training [ RAPIT ] ) with those of physical therapy ( termed usual care [ UC ] ) . METHODS Three hundred nine RA patients were assigned to either the RAPIT program or UC . The primary end points were functional ability ( assessed by the McMaster Toronto Arthritis [ MACTAR ] Patient Preference Disability Question naire and the Health Assessment Question naire [ HAQ ] ) and the effects on radiographic progression in large joints . Secondary end points concerned emotional status and disease activity . RESULTS After 2 years , participants in the RAPIT program showed greater improvement in functional ability than participants in UC . The mean difference in change of the MACTAR Question naire score was 2.6 ( 95 % confidence interval [ 95 % CI ] 0.1 , 5.2 ) over the first year and 3.1 ( 95 % CI 0.7 , 5.5 ) over the second year . After 2 years , the mean difference in change of the HAQ score was -0.09 ( 95 % CI -0.18 , -0.01 ) . The median radiographic damage of the large joints did not increase in either group . In both groups , participants with considerable baseline damage showed slightly more progression in damage , and this was more obvious in the RAPIT group . The RAPIT program proved to be effective in improving emotional status . No detrimental effects on disease activity were found . CONCLUSION A long-term high-intensity exercise program is more effective than UC in improving functional ability of RA patients . Intensive exercise does not increase radiographic damage of the large joints , except possibly in patients with considerable baseline damage of the large joints OBJECTIVE To evaluate the functional , clinical , radiological and quality of life outcomes of a 4-week dynamic exercise programme ( DEP ) in RA . METHODS Patients matched on the principal medico-social parameters were r and omly assigned to either the DEP or the conventional joint rehabilitation group . Primary end point for judging effectiveness was functional status assessed by HAQ . Secondary outcomes included Nottingham Health Profile ( NHP ) , Arthritis Impact Measurement Scale 2-Short Form ( AIMS 2-SF ) and radiological worsening measured by Simple Narrowing Erosion Score ( SENS ) . Clinical evaluation consisted of disease activity score ( DAS 28 ) , cycling aerobic fitness and dexterity . Dexterity was measured using Sequential Occupational Dexterity Assessment ( SODA ) and Duruoz H and Index ( DHI ) . Data were collected at baseline 1 , 6 and 12 months . RESULTS Fifty patients were enrolled . HAQ improved throughout the length of the trial in the DEP group . This improvement was greater in DEP than in the st and ard joint rehabilitation group at 1 month ( -0.2 vs no variation from baseline , P = 0.04 ) , but not at 6 months ( -0.2 vs -0.1 in control group , P = 0.25 ) or 12 months ( -0.1 vs no variation in control group , P = 0.51 ) . DEP improved NHP ( -23 vs + 7 % in control group , P = 0.01 ) and aerobic fitness ( + 0.3 vs + 0.1 km per 5 min in control group , P = 0.02 ) at 1 month but the progress was not statistically significant thereafter . DEP also improved DHI , SODA , DAS 28 and AIMS 2-SF , although not significantly . CONCLUSION DEP was effective on functional status assessed by HAQ , quality of life and aerobic fitness at 1 month |
480 | 27,543,718 | Decreased baseline eGFR is independently associated with increased future myocardial infa rct ion , and the risk increases with advanced renal insufficiency . | BACKGROUND Chronic kidney disease is increasing in prevalence .
The association between low baseline estimated glomerular filtration rate ( eGFR ) and future myocardial infa rct ion has not been comprehensively assessed . | OBJECTIVES The goal of this study was to determine if restenosis is increased in mild and moderate chronic kidney disease ( CKD ) patients after percutaneous coronary intervention ( PCI ) . BACKGROUND Mortality is increased in CKD after PCI . Restenosis may contribute to increased late mortality . METHODS We analyzed 11,187 patients with a creatinine < 1.8 mg/dl from the Prevention of REStenosis with Tranilast and its Outcomes ( PRESTO ) trial , grouped by estimated creatinine clearance ( CrCl ) ( < 60 , 60 to 89 , > 89 ml/min ) . The Cox proportional hazards models investigated the association between CrCl group and death , myocardial infa rct ion , and target vessel revascularization ( TVR ) . Generalized estimating equation regression models determined the association between CrCl group and lesion-specific restenosis . RESULTS At 30 days , there was no difference in myocardial infa rct ion , death , or TVR between the CrCl groups . At nine months , mortality was higher in the lowest CrCl group ( 2.2 % , 1.2 % , 0.8 % ; p < 0.001 ) , which was no longer significant after adjusting for confounding variables . Myocardial infa rct ion and TVR were not different between the groups . In patients undergoing protocol follow-up angiography , restenosis ( > /=50 % ) was not increased with CKD ( 32 % , 32 % , 37 % ; p = 0.02 ) . CONCLUSIONS Mortality nine months after PCI is mildly increased in mild or moderate CKD patients . However , restenosis is not and does not account for the increased mortality Background —Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease ( CKD ) have an increased risk of death after myocardial infa rct ion ( MI ) that is not fully explained by associated comorbidities . Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized . Methods and Results —We calculated the estimated glomerular filtration rate ( eGFR ) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement ( SAVE ) trial subjects . SAVE r and omized post-MI subjects ( 3 to 16 days after MI ) with left ventricular ejection fraction ≤40 % and serum creatinine < 2.5 mg/dL to captopril or placebo . Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR . Subjects with reduced eGFR were older and had more extensive comorbidities . The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74 , 45 to 59 , and < 45 mL · min−1 · 1.73 m−2 ( compared with eGFR ≥75 mL · min−1 · 1.73 m−2 ) was 1.11 ( 0.86 to 1.42 ) , 1.24 ( 0.96 to 1.60 ) and 1.81 ( 1.32 to 2.48 ) , respectively ( P for trend = 0.001 ) . Similar adjusted trends were present for CV mortality ( P=0.001 ) , recurrent MI ( P=0.017 ) , and the combined CV mortality and morbidity outcome ( P=0.002 ) . The absolute benefit of captopril tended to be greater in subjects with CKD : 12.4 versus 5.5 CV events prevented per 100 subjects with ( n=719 ) and without ( n=1464 ) CKD , respectively . Conclusions —CKD was associated with a heightened risk for all major CV events after MI , particularly among subjects with an estimated glomerular filtration rate < 45 mL · min−1 · 1.73 m−2 . R and omization to captopril result ed in a reduction of CV events irrespective of baseline kidney function OBJECTIVES This study sought to determine the independent association of renal insufficiency with cardiovascular risk among women with known coronary heart disease ( CHD ) . BACKGROUND Although patients with end-stage renal disease and proteinuria are at high risk for cardiovascular events , little is known about the cardiovascular risk associated with moderate renal insufficiency . METHODS The Heart and Estrogen/progestin Replacement Study ( HERS ) was a clinical trial among 2,763 women with coronary disease who were r and omized to conjugated estrogen plus progestins or identical placebo and followed for a mean of 4.1 years . Women were categorized as having normal renal function ( creatinine < 1.2 mg/dl ; n = 2,012 ) , mild renal insufficiency ( 1.2 mg/dl to 1.4 mg/dl ; n = 567 ) and moderate renal insufficiency ( > 1.4 mg/dl ; n = 182 ) . We examined the independent association of renal function with incident cardiovascular events including CHD death , nonfatal myocardial infa rct ion , hospitalization for unstable angina , stroke and transient ischemic attacks . RESULTS Compared with women with normal renal function , those with mild and moderate renal insufficiency were older , more likely to be black , have a history of hypertension and diabetes and have higher serum levels of triglycerides and lipoprotein(a ) . After multivariate adjustment , both mild ( relative hazards [ RH ] = 1.24 ; 95 % confidence interval [ CI ] : 1.0 to 1.5 ) and moderate renal insufficiency ( RH = 1.57 ; 95 % CI : 1.2 to 2.1 ) were independently associated with increased risk for cardiovascular events compared with women with normal renal function . CONCLUSIONS Renal insufficiency is an independent risk factor for cardiovascular events in postmenopausal women with known coronary artery disease . Renal function may add helpful information to CHD risk stratification Background Reduced glomerular filtration rate ( GFR ) is associated with increased cardiovascular risk in young and middle aged individuals . Associations with cardiovascular disease and mortality in older people are less clearly established . We aim ed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants r and omized in the Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Methods and Findings Glomerular filtration rate was estimated ( eGFR ) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ( [ 20–40 ] , [ 40–50 ] , [ 50–60 ] ) ≥ 60 ml/min/1.73 m2 . Baseline risk factors were analysed by category of eGFR , with and without adjustment for other risk factors . The associations between baseline eGFR and morbidity and mortality outcomes , accrued after an average of 3.2 y , were investigated using Cox proportional hazard models adjusting for traditional risk factors . We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status . Age , low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol , C-reactive protein ( CRP ) , body mass index , fasting glucose , female sex , histories of hypertension and vascular disease were associated with eGFR ( p = 0.001 or less ) after adjustment for other risk factors . Low eGFR was independently associated with risk of all cause mortality , vascular mortality , and other noncancer mortality and with fatal and nonfatal coronary and heart failure events ( hazard ratios adjusted for CRP and other risk factors ( 95 % confidence intervals [ CIs ] ) for eGFR < 40 ml/min/1.73m2 relative to eGFR ≥ 60 ml/min/1.73m2 respectively 2.04 ( 1.48–2.80 ) , 2.37 ( 1.53–3.67 ) , 3.52 ( 1.78–6.96 ) , 1.64 ( 1.18–2.27 ) , 3.31 ( 2.03–5.41 ) . There were no nominally statistically significant interactions ( p < 0.05 ) between r and omized treatment allocation and eGFR for clinical outcomes , with the exception of the outcome of coronary heart disease death or nonfatal myocardial infa rct ion ( p = 0.021 ) , with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs . Conclusions We have established that , in an elderly population over the age of 70 y , impaired GFR is associated with female sex , with presence of vascular disease , and with levels of other risk factors that would be associated with increased risk of vascular disease . Further , impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes . Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin OBJECTIVES In Incremental Decrease in Endpoints through Aggressive Lipid-lowering ( IDEAL ) , we compared cardiovascular outcomes in patients with and without chronic kidney disease ( CKD ) ( estimated glomerular filtration rate < 60 mL min(-1 ) 1.73 m(-2 ) ) and analysed relationships between lipoprotein components ( LC ) and major coronary events ( MCE ) and other cardiovascular ( CV ) events . DESIGN Exploratory analysis of CV endpoints in a r and omized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE . SETTING S Patients with CKD were compared with the non-CKD patients . Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE . FINDINGS Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality . In patients with CKD , a significant benefit of high dose atorvastatin treatment was found for any CV events , stroke and peripheral artery disease , but not for MCE . However , all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group . Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups . INTERPRETATION Chronic kidney disease was a powerful risk factor for all cardiovascular end-points . The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent . This difference did not result from differential changes in or relations to LC , but limited power may have increased the possibility of chance findings Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To evaluate the association of kidney function with cardiovascular disease and mortality among apparently healthy women . Design Prospect i ve cohort study . Setting Women ’s Health Study , United States . Participants 27 939 female health professionals aged ≥45 who were free of cardiovascular disease and other major disease and who provided a blood sample at study entry . Main outcome measures Time to cardiovascular disease ( non-fatal stroke , non-fatal myocardial infa rct ion , coronary revascularisation procedures , or death from cardiovascular cause ) , specific cardiovascular disease events , and all-cause mortality . End points were confirmed after review of medical records and death certificates . Results Glomerular filtration rate ( GFR ) was estimated with the abbreviated Modification of Diet in Renal Disease Study equation . At baseline , 1315 ( 4.7 % ) women had GFR < 60 ml/min/1.73 m2 . During 12 years of follow-up , 1199 incident cardiovascular disease events and 856 deaths ( 179 from cardiovascular disease ) occurred . Compared with women with GFR ≥90 ml/min/1.73 m2 , the multivariable adjusted hazard ratios for any first cardiovascular disease were 0.95 ( 95 % CI 0.83 to 1.08 ) , 0.84 ( 0.70 to 1.00 ) , and 1.00 ( 0.79 to 1.27 ) among women with GFR of 75 - 89.9 , 60 - 74.9 , and < 60 ml/min/1.73 m2 , respectively ; the equivalent hazard ratios for all cause mortality were 0.93 ( 0.79 to 1.09 ) , 1.03 ( 0.85 to 1.26 ) , and 1.09 ( 0.83 to 1.45 ) . Similar null findings were observed for myocardial infa rct ion , stroke , coronary revascularisation , and non-cardiovascular death . However , an increased risk of death from cardiovascular disease was found among women with GFR < 60 ml/min/1.73 m2 ( hazard ratio 1.68 ( 1.02 to 2.79 ) ) . Conclusions In this large cohort of women , a glomerular filtration rate < 60 ml/min/1.73 m2 was associated with increased risk of cardiovascular disease death but not other cardiovascular disease events or non-cardiovascular disease mortality . We observed no increase in risk of any of the outcomes among women with less severe impairment of kidney function BACKGROUND High C-reactive protein ( CRP ) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure . There are limited data evaluating the relationships between CRP , albumin , and outcomes in chronic kidney disease ( CKD ) stages 3 and 4 . METHODS The Modification of Diet in Renal Disease ( MDRD ) Study was a r and omized controlled trial conducted between 1989 and 1993 . CRP was measured in frozen sample s taken at baseline . Survival status and cause of death , up to December 31 , 2000 , were obtained from the National Death Index . Multivariable Cox models were used to examine the relationship of CRP [ stratified into high CRP > or = 3.0 mg/L ( N= 414 ) versus low CRP<3.0 mg/L ( N= 283 ) ] , and serum albumin , with all-cause and cardiovascular mortality . RESULTS Median follow-up time was 125 months , all-cause mortality was 20 % ( N= 138 ) and cardiovascular mortality was 10 % ( N= 71 ) . In multivariable analyses adjusting for demographic , cardiovascular and kidney disease factors , both high CRP ( HR , 95 % CI = 1.56 , 1.07 - 2.29 ) and serum albumin ( HR = 0.94 per 0.1 g/dL increase , 95 % CI = 0.89 - 0.99 ) were independent predictors of all-cause mortality . High CRP ( HR 1.94 , 95 % CI 1.13 - 3.31 ) , but not serum albumin ( HR 0.94 , 95 % CI 0.87 - 1.02 ) , was an independent predictor of cardiovascular mortality . CONCLUSION Both high CRP and low albumin , measured in CKD stages 3 and 4 , are independent risk factors for all-cause mortality . High CRP , but not serum albumin , is a risk factor for cardiovascular mortality . These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD Kidney dysfunction and high C-reactive protein ( CRP ) levels are independently associated with coronary events . However , it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function . With the use of a prospect i ve , nested , case-control study design , the association among kidney function , inflammatory biomarker levels , and coronary events was studied . A total of 244 women who were participants in the Nurses ' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event ( defined as nonfatal myocardial infa rct ion or death as a result of coronary disease ) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects . Serum creatinine and inflammatory biomarker levels were measured in blood sample s collected in 1989 . Creatinine clearance ( CrCl ) was estimated using creatinine , age , weight , and height . In multivariate analyses , the odds ratio ( OR ) for a coronary event in women with an estimated CrCl < 60 ml/min was 2.33 ( 95 % confidence interval [ CI ] , 1.01 to 5.38 ) compared with those with a CrCl > or = 90 ml/min . When soluble tumor necrosis factor receptor ( sTNFR ) I and II levels were added into this model individually , the observed OR for women with CrCl < 60 ml/min was attenuated . In analyses stratified by estimated CrCl , higher high-sensitivity CRP ( hs-CRP ) , IL-6 , and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or = 74 ml/min but not in women with an estimated CrCl > or = 75 ml/min . The OR per 5-mg/L unit increase in hs-CRP was 1.68 ( 95 % CI , 1.13 to 2.52 ) for women with an estimated CrCl < or = 74 ml/min , compared with 1.23 ( 95 % CI , 0.86 to 1.76 ) and 0.99 ( 95 % CI , 0.76 to 1.29 ) for women with an estimated CrCl 75 to 89 and > or = 90 ml/min , respectively ( P = 0.004 for interaction ) . In conclusion , kidney dysfunction is associated with an increased odds of coronary events , and inflammation , as assessed by higher sTNFR I and II levels , may mediate some of this risk . Higher inflammatory biomarkers levels , specifically , hs-CRP , IL-6 , and sTNFR I and II , were significantly associated with coronary events only in women with reduced kidney function . These findings warrant further investigation in other population A recent report found that chronic kidney disease ( CKD ) increased the risk for coronary heart disease ( CHD ) events in people with anemia but not in those without anemia . This study aim ed to verify these findings in the Blue Mountains Eye Study cohort , a prospect i ve Australian population -based study of 3654 residents aged 49 to 97 yr . Fasting blood sample s were obtained at baseline and confirmed CHD-related deaths over 9 yr with the Australian National Death Index . " Low hemoglobin " was defined as levels in the lowest quintile of the cohort . Body surface area-adjusted GFR was estimated using a variety of methods ( Cockcroft-Gault , abbreviated Modification of Diet in Renal Disease , and Bjornsson equations ) . People with CKD ( GFR < 60 ml/min per 1.73 m2 as estimated using the Cockcroft-Gault equation ) and low hemoglobin ( mean 13.2 g/dl ; range 7.6 to 14.6 g/dl ) had an increased risk for CHD-related death ( multivariable-adjusted hazard risk ratio 1.49 ; 95 % confidence interval 1.08 to 2.06 ) compared with people with CKD but in higher hemoglobin quintiles . This effect was not evident in people without CKD . The interaction between GFR and hemoglobin was significant ( P = 0.05 ) when GFR was estimated using either the Cockcroft-Gault or Bjornsson equations or when serum creatinine instead of GFR was used in the analyses but not when GFR was estimated using the abbreviated Modification of Diet in Renal Disease equation . In conclusion , this study found that low hemoglobin , even within the normal range , together with CKD increased the risk for CHD-related death BACKGROUND Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein ( CRP ) . The aim of this study was to determine whether CRP is a marker of overall and cardiovascular morbidity in chronic kidney disease ( CKD ) 3 - 5 patients . METHODS 90 chronic kidney disease 3 - 5 patients were prospect ively followed during a period of 24 months . Cardiovascular events were defined as episodes of myocardial infa rct ion , stroke , angina pectoris and /or peripheral vascular disease . Morbidity was analyzed in terms of both the need for hospital admission ( > 48 h ) and total number of days of hospitalization during the follow-up period . CRP was stratified into tertiles of low ( < 8 mg/l ) , medium ( 8 - 10.5 mg/l ) and high ( > 10.5 mg/l ) . The use of some drugs such as ACE inhibitor and ARAII were also recorded . RESULTS During the follow-up period , 23 patients ( 25 % ) required hospital admission . New cardiovascular events were observed in 20 patients ( 22 % ) , 10 patients died during the follow-up . Adjusted Cox regression analysis revealed that CRP and serum albumin significantly predicted the risk of cardiovascular events . Similarly , high CRP , low serum albumin and low hemoglobin levels predicted morbidity as measured by the number of hospitalizations . Hemoglobin and albumin levels were lower in patients with high CRP ( > or = 10.5 mg/l , highest tertile ) as compared with low CRP levels ( < or = 8 mg/l , lowest tertile ) . Patients receiving treatment with angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin II receptor Type 1 antagonist ( ARA-II ) had significantly lower levels of CRP than those who were not under such treatment ( n = 46 , CRP = 8.7 ( 5.1 - 29.8 ) vs n = 44 , CRP = 10.4 ( 6.1 - 37.2 ) , p < 0.05 ) ( Figure 1 ) . CONCLUSIONS Our results show that CRP and low albumin , markers of inflammation , predict cardiovascular events and morbidity in CKD 3 - 5 patients before initiation of chronic hemodialysis BACKGROUND Whether estimated glomerular filtration rate ( eGFR ) calculated using the Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) Study equation ( eGFRCKDEPI ) improves risk prediction compared to that calculated using the Modification of Diet in Renal Disease ( MDRD ) study equation ( eGFRMDRD ) has not been examined in a prospect i ve study in Japanese people . METHODS AND RESULTS Participants ( n=24,560 ) were divided into 4 stages ( 1 , ≥90 ; 2 , 60 - 89 ( reference ) ; 3a , 45 - 59 ; 3b+ < 45 ml·min(-1)·1.73 m(-2 ) ) according to eGFRCKDEPI or eGFRMDRD . Endpoints were all-cause death , myocardial infa rct ion ( MI ) and stroke . Area under the receiver operating characteristic curves ( 95 % confidence intervals ) for predicting all-cause death , MI and stroke by eGFRCKDEPI vs. eGFRMDRD were 0.680 ( 0.662 - 0.697 ) vs. 0.582 ( 0.562 - 0.602 ) ; 0.718 ( 0.665 - 0.771 ) vs. 0.642 ( 0.581 - 0.703 ) ; and 0.656 ( 0.636 - 0.676 ) vs. 0.576 ( 0.553 - 0.599 ) , respectively . Multivariate-adjusted Cox regression and Poisson regression analysis results were similar for adjusted incidence rates and adjusted hazard ratios in each corresponding stage between the 2 models and no differences were found in model assessment parameters . Net reclassification improvement ( NRI ) for predicting all-cause death , MI and stroke were estimated to be 6.7 % ( P<0.001 ) , -1.89 % ( P=0.029 ) and -0.20 % ( P=0.421 ) , respectively . CONCLUSIONS Better discrimination was achieved using eGFRCKDEPI than eGFRMDRD on univariate analysis . NRI analysis indicated that the use of eGFRCKDEPI instead of eGFRMDRD offered a significant improvement in reclassification of death risk OBJECTIVE To define the optimal glomerular filtration rate ( GFR ) cut off for discriminating the risk of myocardial infa rct ion or cardiovascular death . DESIGN Prospect i ve longitudinal observational study . SETTING A community-based cohort . PARTICIPANTS A total of 2176 nondiabetic 50-year-old men without cardiovascular disease . METHODS The men were followed until age 70 . GFR was estimated at baseline using the Cockcroft-Gault formula . The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infa rct ion and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement ( IDI ) . MAIN OUTCOME MEASURES Fatal or nonfatal myocardial infa rct ion , cardiovascular death . RESULTS During follow-up , 264 men experienced a fatal or nonfatal myocardial infa rct ion , and 218 died of cardiovascular disease . The IDI-defined optimal GFR cut offs in this study were 98 mL min(-1 ) for discriminating myocardial infa rct ion risk and 92 mL min(-1 ) for discriminating risk of cardiovascular death . In Cox proportional hazard models adjusting for established risk factors , the myocardial infa rct ion risk was substantially higher in men with GFR below versus above 98 mL min(-1 ) [ hazard ratio ( HR ) 1.7 , 95 % confidence interval ( CI ) 1.3 - 2.3 , P < 0.001 ] , and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min(-1 ) ( HR 2.1 , 95 % CI 1.5 - 3.0 , P < 0.001 ) . CONCLUSION The GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested |
481 | 27,986,396 | Limitations : Data base studies might not fully account for confounders , result ing in overestimates of the risk impact of comorbidities .
Conclusions : Presenting attributable risk in the form of the number needed to harm provides a clearer picture of the magnitude of risk and a basis for wiser medical decision making and patient education | Background : Psoriasis is associated with numerous comorbidities , often reported in terms of relative risk .
Both doctors and the general population tend to overestimate the effects of exposures when presented in relative terms , leading to anxiety and potentially poor treatment decisions .
Absolute risks might provide a better basis for risk assessment .
Objective : To characterize and compare relative and absolute risks of comorbidities in patients with psoriasis . | Background Psoriasis is an immunoinflammatory disease associated with cardiovascular risk factors , atherothrombotic events , and hypercoagulability . Venous thromboembolism ( VTE ) is potentially lethal and shares risk factors with psoriasis , but the risk of VTE associated with psoriasis is unknown . The present study investigated the potential association between psoriasis and VTE . Methods and Findings Information from nationwide prospect ively recorded registers of hospitalization , drug dispensing from pharmacies , socio-economic data , and causes of death was linked on an individual level . In an unselected nationwide cohort , we used multivariate Poisson regression models controlling for age , gender , comorbidity , concomitant medication , socio-economic data , and calendar year , to assess the risk of VTE associated with psoriasis . A total of 35,138 patients with mild and 3,526 patients with severe psoriasis were identified and compared with 4,126,075 controls . Patients with psoriasis had higher incidence rates per 1000 person-years of VTE than controls ( 1.29 , 1.92 , and 3.20 for controls , mild psoriasis , and severe psoriasis , respectively ) . The rate ratio ( RR ) of VTE was elevated in all patients with psoriasis with RR 1.35 ( 95 % confidence interval [ CI ] 1.21–1.49 ) and RR 2.06 ( CI 1.63–2.61 ) for mild and severe psoriasis , respectively . Exclusion of patients with malignancies , and censoring of patients undergoing surgery did not alter the results . Conclusion This nationwide cohort study indicates that patients with psoriasis are at increased risk of VTE . The risk was highest in young patients with severe psoriasis . Physicians should be aware that patients with psoriasis may be at increased risk of both venous and arterial thromboembolic events BACKGROUND Psoriasis is a chronic inflammatory disease and is associated with cardiovascular events . Little is known about sub clinical myocardial dysfunction and potential changes in myocardial function during anti-inflammatory treatment in these patients . We prospect ively studied left ventricular function in patients with severe psoriasis who initiated biologic therapy . METHODS Between November 1 2013 and May 31 2014 the study subjects underwent physical , laboratory and comprehensive echocardiographic examination at baseline and after 3 months of treatment . Pearson correlation coefficients and Student 's t-test were applied to assess changes in diastolic function ( defined as the E/e ' ratio ) and global longitudinal strain ( GLS ) . RESULTS Eighteen patients with severe psoriasis treated with biologic therapy with a mean follow-up of 85.6 ± 18.2 days were included . The patients had a baseline psoriasis area and severity index ( PASI ) of 12.0 ± 4.1 and normal left ventricular ejection fraction [ ( LVEF ) 56.3 ± 3.8 % ] , diastolic dysfunction ( E/e ' 8.1 ± 2.1 ) and GLS ( -16.8 ± 2.1 % ) . At follow-up , an improvement ( baseline vs. follow-up ) of PASI ( 12.0 ± 4.1 vs. 2.7 ± 3.1 , P < 0.001 ) , E/e ' ( 8.1 ± 2.1 vs. 6.7 ± 1.9 , P ≤ 0.001 ) and GLS ( -16.8 ± 2.1 vs. -18.3 ± 2.3 % , P < 0.001 ) were recorded . No changes were demonstrated in LVEF ( 56.3 ± 3.8 vs. 56.8 ± 3.3 % , P = 0.31 ) , body mass index ( 30.9 ± 5.7 vs. 31.0 ± 5.8 kg/m(2 ) , P = 0.90 ) , mean arterial blood pressure ( 103.1 ± 8.5 vs. 103.7 ± 10.8 mmHg , P = 0.74 ) . Likewise , no changes were seen in total cholesterol , low density lipoprotein cholesterol , high density lipoprotein cholesterol , estimated glomerular filtration rate and glycosylated haemoglobin . CONCLUSION In patients with severe psoriasis treatment with biologic therapy was associated with improved PASI and amelioration of myocardial dysfunction OBJECTIVES To assess the extent to which abstract s of method ological research , initially presented at meetings on systematic review s , have gone on to be published as full articles . METHODS Full publication was assessed in three ways : a search was carried out of The Cochrane Library ; a search was conducted using MEDLINE ; and a question naire was sent to the contact author of each abstract . RESULTS Approximately half of the abstract s had not been , or were unlikely ever to be , published in full . CONCLUSIONS The rate of full publication of abstract s related to the methodology of systematic review s seems similar to that for r and omized trials AIMS Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation ( AF ) and ischaemic stroke . We therefore investigated the risk of these endpoints in patients with psoriasis . METHODS AND RESULTS Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospect ively recorded registers . Multivariable Poisson 's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke . A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals , i.e. , the reference population . In patients with mild psoriasis , the adjusted rate ratios ( RRs ) for AF were 1.50 ( 1.21 - 1.86 ) and 1.16 ( 1.08 - 1.24 ) in patients aged < 50 and ≥50 years , respectively . Patients with severe psoriasis had a higher risk of AF with RRs 2.98 ( 1.80 - 4.92 ) in patients aged < 50 years and 1.29 ( 1.01 - 1.65 ) in patients aged ≥50 years . Patients with psoriasis also demonstrated a disease severity-dependent increased risk of ischaemic stroke , i.e. RRs 1.97 ( 1.66 - 2.34 ) and 2.80 ( 1.81 - 4.34 ) in patients aged < 50 years with mild and severe psoriasis , and RRs 1.13 ( 1.04 - 1.21 ) and 1.34 ( 1.04 - 1.71 ) in patients aged ≥50 years with mild and severe psoriasis , respectively . A range of sensitivity analyses yielded comparable results . CONCLUSION Psoriasis is associated with increased risk of AF and ischaemic stroke . These novel results add to a growing body of evidence , suggesting that patients with psoriasis could be considered at increased cardiovascular risk OBJECTIVE To compare clinicians ' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome . DESIGN Survey , with r and om allocation of two question naires . SETTING Toronto teaching hospitals . RESPONDENTS Convenience sample of 100 faculty and housestaff in internal medicine and family medicine . INTERVENTION One question naire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events ; the other showed the same end points as relative differences . Both question naires included a fourth " trial , " showing person-years of treatment needed to prevent one myocardial infa rct ion . MAIN OUTCOME MEASURE The " trials " were each rated on an 11-point scale , from treatment " harmful " to " very effective . " RESULTS Respondents ' ratings of effectiveness varied with the end point . Controlling for end point , ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions ( P < 0.001 ) ; however , no end-point difference was more than 0.6 scale points . For a " trial " reporting that 77 persons were treated for 5 years to prevent one myocardial infa rct ion , mean ratings were 2.3 or 1.8 scale points lower , respectively ( both P < 0.001 ) , than when the same data were shown as relative or absolute risk reductions . CONCLUSIONS Clinicians ' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements , by end-point emphasis , and , above all , by underuse of summary measures that relate treatment burden to therapeutic yields in a clinical ly relevant manner Clinical trials may lead to conflicting results . We studied how different ways of reporting results affected physicians ' recommendations . A question naire distributed to 148 general practitioners presented results of a clinical trial where a reduction of cardiac events and an increase of mortality was reported . Results were shown in four different ways -- relative risk reduction , absolute risk reduction , percentages of event-free patients , number needing to be treated to prevent an event -- as if they derived from different trials . A fifth presentation was the reduced rate of cardiac events along with the increased rate of mortality . Physicians were asked to estimate how much they would be willing to prescribe each drug . The mean agreement of physicians ' decisions was 77 (28)% for relative risk reduction , 24 (28)% for absolute risk reduction , 37 (37)% for different percentages event-free patients , 34 (34)% for number need to treat , and 23 (28)% for events reduction and mortality for increase ( p < 0.001 relative risk vs others ) . The method of reporting trial results and the completeness of information in the case of controversial results affects physicians willingness to prescribe Abstract Objective : To determine whether the reporting of study results by using reductions in relative or absolute risk and the number needed to treat affects the views of physicians about the effectiveness of drugs to lower lipid concentrations and decisions about treatment . Design : R and om allocation of two question naires presenting the results of three end points of the Helsinki heart study as results from separate trials by using reduction in either relative or absolute20risk . In both question naires one end point was also presented by showing person years of treatment20needed to prevent one myocardial infa rct ion . The effectiveness of lipid lowering drugs was assessed for all end points on an 11 point scale . For each study result the likelihood to treat hypercholesterolaemia of 7.5 mmol/l in a healthy man had to be indicated on a seven point scale . Subjects : R and om sample of 802 internists and general practioners representative of providers of primary care in Switzerl and . Results - The response rate was 69.6 % ( 558 ) . For the prevention of fatal and non-fatal myocardial infa rct ion the mean ratings of effectiveness of lipid lowering drugs were 0.45 ( 95 % confidence interval 0.21 to 0.69 ) and 1.39 ( 1.09 to 1.68 ) scale points lower when the reduction of absolute risk or number needed to treat were reported instead of the relative risk reduction ( both P<0.001 ) . Physicians receiving trial results for identical end points in form of absolute reduction of risk or number needed to treat were less inclined to treat hypercholesterolaemia ( both P<0.001 ) . Conclusions : Physicians ' views of the effectiveness of lipid lowering drugs and the decision to prescribe such drugs is affected by the predominant use of reduction of relative risk in trial reports and advertisements |
482 | 25,056,719 | The available data are limited , but suggest that neither form of surgical approach be it laparoscopy or open surgery demonstrate superiority in preservation of sexual and bladder function . | There have been conflicting opinions regarding the superiority of open and laparoscopic surgery in preserving bladder and sexual function after rectal cancer surgery .
This systematic review and meta- analysis aims to pool the available data comparing the impact of surgical approaches on postoperative sexual and urinary function . | Background Sexual and urinary dysfunction is an established risk after pelvic surgery . Studies examining sexual and urinary function following laparoscopic and open rectal surgery give conflicting evidence for outcomes . The purpose of this study was to analyse the impact of the surgical technique on functional outcomes following laparoscopic or open resection for rectal cancer patients in a high-volume laparoscopic unit . Methods All patients who underwent elective laparoscopic or open surgery for rectal cancer between September 2006 and September 2009 were identified from a prospect ively collated data base . Vali date d st and ardized postal question naires were sent to surviving patients to assess their postoperative sexual and urinary function . The functional data were then quantified using previously vali date d indices of function . Results A total of 173 patients were identified from the data base , of whom 144 ( 83 % ) responded to the question naire-based study . Seventy-eight respondents had undergone laparoscopic rectal resection ( 49 men and 29 women ) , and 65 had an open procedure ( 41 men and 24 women ) . Both open surgery and laparoscopic surgery were associated with deterioration in urinary and sexual function . With regard to urinary function , there was no difference in the deterioration in open and laparoscopic groups in either gender . With regard to sexual function , in males one component of sexual function , namely , the incidence of successful penetration , showed less deterioration in the laparoscopic group ( p = 0.04 ) . However , in females , laparoscopic surgery was associated with significantly better outcomes in all aspects of sexual activity , specifically sexual arousal ( p = 0.005 ) , lubrication ( p = 0.001 ) , orgasm ( p = 0.04 ) , and the incidence of dyspareunia ( p = 0.02 ) . Conclusion Laparoscopic total mesorectal excision for rectal cancer is associated with significantly less deterioration in sexual function compared with open surgery . This effect is particularly pronounced in women Bladder and sexual dysfunction , secondary to pelvic nerve injury , are recognized complications of rectal resection . This study investigated the frequency of these complications following laparoscopically assisted and conventional open mesorectal resection for cancer Objective To assess long-term quality of life in a population -based sample of rectal cancer patients . Summary Background Data Quality of life in rectal cancer patients who suffer reduced bowel and sexual function is very important . Few studies , however , have long term follow-up data or sufficient sample sizes for reliable comparisons between operation groups . Patients and Methods A 4-year prospect i ve study of rectal cancer patients ’ quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-30 and CR38 question naires . Results A total of 329 patients returned question naires . Overall , anterior resection patients had better quality of life scores than abdominoperineal extirpation patients . High-anterior resection patients had significantly better scores than both low-anterior resection and abdominoperineal extirpation patients . Low-anterior resection patients , however , overall had a better quality of life than abdominoperineal extirpation patients , especially after 4 years . Abdominoperineal extirpation patients ’ quality of life scores did not improve over time . Stoma patients had significantly worse quality of life scores than nonstoma patients . Quality of life improved greatly for patients whose stoma was reversed . Conclusions Anterior resection and nonstoma patients , despite suffering micturition and defecation problems , had better quality of life scores than abdominoperineal extirpation and stoma patients . Comparisons between abdominoperineal extirpation and anterior resection patients should consider the effect of temporary stomas . Improvements in quality of life scores over time may be explained by reversal of temporary stomas or physiologic adaptation Only few studies have investigated the impact of surgery for rectal cancer on sexual function . Little of that research included quality of life ( QoL ) aspects and hardly any study analyzed the impact of age , gender and type of surgery on sexual function . The aim of the presented study was to address these issues . Over a 5 y period , EORTC-QLQ-C-30 and a tumor-specific module were prospect ively administered to patients before surgery , at discharge , 3 , 6 , 12 and 24 months postoperatively . Comparisons were made between patients receiving abdominoperineal resection ( APR ) , anterior resection ( AR ) with or without Pouch and Sigmoid resection . Furthermore , effects of surgery on female and male patients , and age groups were analyzed . A total of 819 patients participated in the study : 412 were males and 407 were females . The groups were comparable in terms of adjuvant treatment , tumor stage and histology . Patients after APR and AR with Pouch had worst sexual function . Men reported significantly more difficulties with sexual enjoyment ; furthermore , over time , sexual problems created high levels of strain in men that were worse than baseline levels in the early postoperative period . These problems tended to remain . Patients aged 69 y and younger scored higher for problems with loss of sexual function and sexuality-related strain than patients aged 70 y and older . The findings in this study confirm that QoL changes postsurgery and that factors like type of surgery , gender and age have tremendous impact on sexual function and sexual enjoyment . APR and AR with Pouch affect sexual function more than AR and resection of the lower sigmoid . Through impaired sexual enjoyment , men are put more under strain than women . Patients aged 69 y and younger experience more stress through deteriorated sexual function Background Sexual function may be harmed after treatment for rectal cancer . This study aim ed to evaluate prospect ively the incidence of sexual dysfunction after rectal cancer treatment and to compare the effects of laparoscopic and traditional open approaches in terms of postoperative sexual function . Methods Baseline and 3- , 6- , and 12-month assessment s of sexual dysfunction using the International Index of Erectile Function ( IIEF ) and its specific domains prospect ively took place for 56 patients who underwent rectal cancer surgery ( 38 open vs. 18 laparoscopic procedures , 38 low anterior vs. 18 abdominoperineal resections ) . The preliminary results are presented . Results The average total IIEF and isolated IIEF response domain scores were significantly decreased after surgery ( p < 0.01 ) except for the intercourse satisfaction and overall satisfaction scores at 12 months . An improvement in IIEF scores was observed between the 3- and 6-month assessment points ( p < 0.01 ) except for the erectile function and orgasmic function scores . No significant differences were observed between the open and laparoscopic groups in the total IIEF and domain scores preoperatively and at the 3- and 6-month assessment points . The rates of sexual dysfunction did not differ significantly preoperatively or at 3 months postoperatively when open and laparoscopic procedures were compared , although there was a trend in favor of laparoscopic surgery at 6 months ( p = 0.076 ) . The baseline IIEF score and the baseline , 3- , and 6-month sexual desire scores were better ( p = 0.035 , 0.004 , 0.017 , and 0.061 , respectively ) in the low anterior resection group than in the abdominoperineal resection group . Conclusions Rectal cancer resections were postoperatively associated with a significant reduction in IIEF scores and high rates of sexual dysfunction at 3 and 6 months . The IIEF and domain scores at different assessment points were comparable between the laparoscopic and open surgery groups . Extending the monitoring period and adding more patients in this ongoing prospect i ve study will further eluci date postoperative sexual dysfunction after rectal cancer surgery AIMS To evaluate the health-related quality of life ( HRQoL ) outcomes in patients undergoing laparoscopic total mesorectal excision ( LTME ) with anal sphincter preservation ( ASP ) for low rectal cancers . METHODS Patients undergoing LTME with ASP or open procedures ( OTME ) for low rectal cancers were prospect ively followed up . All patients were treated in curative attempt and were free of local recurrence during the study . HRQoL was assessed by question naires during 3 - 6 months , 12 - 18 months , and 2 - 5 years after surgery . RESULTS From June 2001 to March 2006 , 125 patients undergoing LTME and 103 undergoing OTME were included in this study . In contrast to OTME patients , the LTME ones showed significantly better physical function during 3 - 6 months after surgery , less micturition problems within 12 - 18 months , less male sexual problems and better sexual function during 12 - 18 months after surgery , with better sexual enjoyment after 24 months postoperatively . Both groups showed significant improvement in most subscales from the first to the second assessment , and an improvement in sexual enjoyment from the second to the third assessment . The sexual function , micturition problems and male sexual problems in the LTME group significantly improved from the first to the second assessment , whereas the sexual function in the OTME group improved from the second to the third assessment . CONCLUSIONS Patients undergoing LTME for low rectal cancers can achieve superior postoperative HRQoL than patients undergoing OTME , with superior physical function , micturition function , overall sexual and male sexual functions in the short term , and better sexual enjoyment in the long term . The HRQoL of both LTME and OTME patients may be expected to improve over time , particularly over the first postoperative year BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent |
483 | 22,143,219 | CONCLUSION Finding suggests that psychological distress in forms of depression , anxiety , anger , and hostility impact unfavorably on recurrent cardiac events in CAD patients | PURPOSE The purpose of this study was to determine whether psychological distress is an independent risk factor for recurrent cardiac events in patients with coronary artery disease ( CAD ) . | OBJECTIVE The reporting of depressive symptoms following myocardial infa rct ion may be confounded by complaints originating from the myocardial infa rct ion . Therefore , it is difficult to estimate the effects of post-myocardial infa rct ion depression and its treatment on cardiovascular prognosis . The authors ' goal was to study the relationship between depressive symptom dimensions following myocardial infa rct ion and both somatic health status and prospect i ve cardiovascular prognosis . METHOD In two studies of myocardial infa rct ion patients ( N=494 and 1,972 ) , the Beck Depression Inventory was used to determine the dimensional structure of depressive symptoms following myocardial infa rct ion . Three symptom dimensions-somatic/affective , cognitive/affective , and appetitive-were compared with baseline left ventricular ejection fraction , Charlson comorbidity index , Killip class , and previous myocardial infa rct ion . The relationship between depressive symptom dimensions and prospect i ve cardiovascular mortality and cardiac-related readmissions was also examined ( mean follow-up duration = 2.5 years ) . RESULTS Somatic/affective symptoms were associated with poor health status ( left ventricular ejection fraction , Charlson comorbidity index , Killip class , and previous myocardial infa rct ion ) and predicted cardiovascular mortality and cardiac events . Cognitive/affective symptoms were only marginally associated with somatic health status and not with cardiovascular death and cardiac events . Appetitive symptoms were related to somatic health status but did not predict cardiovascular death or cardiac events . CONCLUSIONS Somatic/affective depressive symptoms following myocardial infa rct ion were confounded by somatic health status yet were prospect ively associated with cardiac prognosis even after somatic health status was controlled . Cognitive/affective depressive symptoms were only marginally related to health status and not to cardiac prognosis . These findings suggest that treatment of depression following myocardial infa rct ion might improve cardiovascular prognosis when it reduces somatic/affective symptoms BACKGROUND Individual symptoms of post-myocardial infa rct ion ( MI ) depression may be differentially associated with cardiac prognosis , in which somatic/affective symptoms appear to be associated with a worse cardiovascular prognosis than cognitive/affective symptoms . These findings hold important implication s for treatment but need to be replicated before conclusions regarding treatment can be drawn . We therefore examined the relationship between depressive symptom dimensions following MI and both disease severity and prospect i ve cardiac prognosis . METHOD Patients ( n=473 ) were assessed on demographic and clinical variables and completed the Beck Depression Inventory ( BDI ) within the first week of hospital admission for acute MI . Depressive symptom dimensions were associated with baseline left ventricular ejection fraction ( LVEF ) and prospect i ve cardiac death and /or recurrent MI . The average follow-up period was 2.8 years . RESULTS Factor analysis revealed two symptom dimensions -- somatic/affective and cognitive/affective -- in the underlying structure of the BDI , identical to previous results . There were 49 events attributable to cardiac death ( n=23 ) or recurrent MI ( n=26 ) . Somatic/affective ( p=0.010 ) but not cognitive/affective ( p=0.153 ) symptoms were associated with LVEF and cardiac death/recurrent MI . When controlling for the effects of previous MI and LVEF , somatic/affective symptoms remained significantly predictive of cardiac death/recurrent MI ( hazard ratio 1.31 , 95 % confidence interval 1.02 - 1.69 , p=0.038 ) . Previous MI was also an independent predictor of cardiac death/recurrent MI . CONCLUSIONS We confirmed that somatic/affective , rather than cognitive/affective , symptoms of depression are associated with MI severity and cardiovascular prognosis . Interventions to improve cardiovascular prognosis by treating depression should be targeted at somatic aspects of depression BACKGROUND Trait anger , hostility , and serum level of homocysteine are associated with recurrent cardiac events after percutaneous coronary interventions . However , whether trait anger or hostility influences the association between serum level of homocysteine and recurrent cardiac events is unknown . OBJECTIVES To examine the relationships among trait anger , hostility , serum level of homocysteine , and recurrent cardiac events after percutaneous coronary interventions . METHODS This prospect i ve study included 135 consecutive patients ( 68 % male , mean age 61 [ SD , 10 ] years ) undergoing percutaneous coronary interventions during an index hospitalization . Trait anger and hostility were measured with the Spielberger Trait Anger Scale and the Cynical Hostility Scale , respectively . Blood sample s were obtained to measure serum levels of total cholesterol , triglycerides , high- and low-density lipoprotein cholesterol , and homocysteine . Recurrent cardiac events ( emergency department visits and rehospitalization ) were noted for 6 months after discharge and confirmed by review of hospital records . Hierarchical Cox hazard regression was used for statistical analysis . RESULTS Trait anger ( hazard ratio = 1.11 , 95 % confidence interval = 1.03 - 1.20 ) and homocysteine level ( hazard ratio = 1.10 , 95 % confidence interval = 1.01 - 1.21 ) were independent predictors of recurrent cardiac events after other risk factors were controlled for . Patients with high trait anger ( score > or = 24 ) and high serum level of homocysteine ( > or = 11.3 mumol/L ) had the shortest time to recurrent cardiac events ( P = .01 ) . CONCLUSION Trait anger had a combined effect on the link between serum level of homocysteine and recurrent cardiac events . Interventions to reduce trait anger may improve health outcomes by influencing both trait anger and homocysteine level Psychosocial variables predict the recurrence of clinical events in symptomatic patients , controlling for measures of disease severity . The Cardiac Arrhythmia Suppression Trial-1 , a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infa rct ion patients , allowed a prospect i ve test of the relationship of distress , perceived support , social interaction , life stress , and other variables , to mortality , adjusting statistically for ejection fraction , arrhythmia rates , and other known risk factors for coronary heart disease . Results indicated that the treatment medications , encainide and flecainide , were powerful predictors of mortality . Although the psychosocial variables were significant as univariate predictors , these variables were not significant as predictors in a multivariate model that included drug treatment . When the data analysis was restricted to patients r and omized to placebo , thereby eliminating the antiarrhythmic drug effect , the level of perceived social support was a significant multivariate predictor of mortality , adjusting for measures of disease severity . The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46 , based on the multivariate model |
484 | 28,653,390 | Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day .
Acetazolamide is associated with an increased risk of paraesthesia , although there are few reports about other adverse events from the available evidence . | BACKGROUND High altitude illness ( HAI ) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres ( 8202 feet ) .
Acute hypoxia , acute mountain sickness ( AMS ) , high altitude cerebral oedema ( HACE ) and high altitude pulmonary oedema ( HAPE ) are reported as potential medical problems associated with high altitude .
In this review , the first in a series of three about preventive strategies for HAI , we assess the effectiveness of six of the most recommended classes of pharmacological interventions .
OBJECTIVES To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI . | The mechanism of high altitude headache ( HAH ) remains unknown . The aim of this study was to determine experimentally whether optic nerve sheath diameter ( ONSD ) , as an indicator of intracranial pressure , is related to HAH . Following sea level measurements at 3 and 12 hours ( SL ) , 23 subjects were passively transported to high altitude ( 3777 m , HA ) via cable car . HAH , ONSD , arterial oxygen saturation ( Spo(2 ) ) , and fluid balance were determined at 3 , 12 , 24 , and 36 hours . After 12 hours exposure to HA , subjects were classified by visual analogue scale ( VAS ) as either HAH positive ( HAH+ ) or HAH negative ( HAH- ) . Acetazolamide ( 250 mg ) or placebo was then r and omly prescribed at 15 , 20 , and 28 hours . Outcome means were compared via analysis of variance , and relationships between variables were analyzed by longitudinal regression . Acetazolamide had no statistically significant effect on HAH ( p=0.63 ) or ONSD ( p=0.98 ) , but produced a negative fluid balance ( p<0.01 ) ( and also increased Spo(2 ) in exploratory analyses ) . Spo(2 ) was lower in HAH+ than HAH- [ 85 (3)% versus 88 (2)% , p=0.03 ) . Nevertheless , ONSD increased similarly in HAH+ and HAH- ( interaction p=0.90 ) . ONSD also remained significantly elevated above SL values for the entire HA period [ SL , 5.2 ( 0.5 ) versus HA , 5.6 ( 0.5 ) mm , p<0.01 ] , despite headache resolving with acclimatization [ VAS : SL , 1/100 ( 3 ) mm versus HA 3 h , 9/100 ( 13 ) ; 12 h , 10/100 ( 14 ) ; 24 h , 8/100 ( 12 ) ; 36 h , 1/100 ( 4 ) mm , p<0.01 ] . Furthermore , HAH was significantly correlated with Spo(2 ) ( β=-1.39 , p<0.01 ) but not with ONSD ( β=0.59 , p=0.57 ) . These data do not support that intracranial pressure is associated with the development or amelioration of mild HAH . Clinical trial registration NCT01288781 Our purpose was to study the preventive effect of the calcium channel blocker flunarizine on headache , postural ataxia , and memory deficits occurring during decompression to high altitude in a r and omized , placebo-controlled , double-blind study . After 7-day pretreatment with the study drugs , 20 healthy men were investigated at 490 m and 0.5 , 2 , 4 , and 6 h later at a simulated altitude of 4559 m. Headache severity was evaluated on a 4-point scale . Sway path and anteroposterior and lateral sway were recorded with open and closed eyes by static posturography . Short- and long-term memory was studied by testing the recall of verbal and figural material immediately and 2 h after presentation , respectively . Blood pressure ( BP ) and arterial oxygen saturation ( Sa(O2 ) ) were also assessed . Headache scores showed a trend to be lower in the flunarizine group that was significant after 4 and 6 h. Headache scores expressed as difference from baseline values showed a nonsignificant trend to be lower at 4 and 6 h in subjects treated with flunarizine . Postural stance , memory , BP , and Sa(O2 ) were similar in both treatment groups . Although the low number of investigated subjects may have prevented the detection of a significant therapeutic effect of flunarizine , the present data do not show that flunarizine is effective for prevention of headache , postural ataxia , and neurocognitive deficits occurring at simulated high altitude BACKGROUND Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it . Among the latter , the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role ; a defect of this mechanism may predispose patients to pulmonary edema . Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models . METHODS In a double-blind , r and omized , placebo-controlled study , we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes ( 4559 m , reached in less than 22 hours ) in 37 subjects who were susceptible to high-altitude pulmonary edema . We also measured the nasal transepithelial potential difference , a marker of the transepithelial sodium and water transport in the distal airways , in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition . RESULTS Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent , from 74 percent with placebo to 33 percent ( P=0.02 ) . The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible ( P<0.001 ) . CONCLUSIONS Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema . Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema . These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy OBJECTIVES To quantify the changes in ventilatory response and arterial blood gases in healthy male volunteers on acute ascent to 4578 meters altitude along with evaluating the role of acetazolamide and dexamethasone prophylaxis in acclimatisation . METHODS Forty four lowl and er male subjects participated as two groups in the study . Twenty four lowl and er healthy male adults ( age mean + /- SE 27.8 + /- 1.24 years ) comprised the non-acclimatised group . They were sub grouped in a double blind fashion into four . Each subgroup ( n=6 ) received placebo ( multivitamin ) or acetazolamide ( 250 mg ) or dexamethasone ( 4 mg ) or combined regimen of the two drugs twice daily for 5 days commencing 24 hours before ascent . The volunteers reached the altitude of 4578 meters within a span of one day . The second group ( acclimatised ) comprised of age and height matched twenty volunteers who had arrived 4 and 8 weeks earlier at the same altitude . Arterial PO2 , PCO2 , SO2 and minute respiratory rate pH were measured . The pulmonary functions ( FVC , % FEV1 PEF , FEF(25 - 75 % ) and MVV ) were recorded by Compact Spirometer ( Vitalograph ) . Pre and post ascent measurements were carried out in non-acclimatised group whereas one measurement of the same parameters were made in acclimatised group . RESULTS The study revealed a significant increase in respiratory rate min-1 after 24 hours of ascent along with reduction in PaO2 and SaO2 . The gradual increase in PaO2 and SaO2 and reduction in PaCO2 was observed after 4 weeks at the same altitude . The reduction in FVC , % FEV1 , PEF , FEF(25 - 75 % ) and MW were recorded in our subjects after 24 hours of acute ascent . Nevertheless , all pulmonary parameters in volunteers having 8 weeks of stay at 4578 m altitude , were found equivalent to the non-acclimatised group . The greater increase in minute respiratory rate , PaO2 , SaO2 and pulmonary functions was found in volunteers taking acetazolamide . CONCLUSION It is concluded that hyperventilation and increase in lung volumes are the adaptive pulmonary responses which help in improving levels of PaO2 and SaO2 . The acetazolamide-dexamethasone prophylaxis appears beneficial in promoting pulmonary acclimatisation during hypobaric hypoxia Context Very few trials have evaluated ways to prevent high-altitude pulmonary edema ( HAPE ) . Contribution In this double-blind trial , 29 adults with a history of HAPE were r and omly assigned to receive prophylactic tadalafil , dexamethasone , or placebo during a 24-hour ascent and 2-day stay at 4559 m. Compared with placebo recipients , adults taking dexamethasone less often experienced acute mountain sickness and those taking either dexamethasone or tadalafil less often had HAPE . Caution s The trial involved a small number of selected adults who rapidly ascended to a high altitude . Implication s Either tadalafil or dexamethasone might help prevent HAPE in mountaineers with a history of pulmonary edema . The Editors Rapid ascent to altitudes greater than 2500 m may cause acute mountain sickness ( AMS ) and high-altitude pulmonary edema ( HAPE ) . In nonacclimatized mountaineers , the prevalences of AMS and HAPE at 4559 m are approximately 50 % and 4 % , respectively ( 1 ) . Individual susceptibility , rate of ascent , and preexposure to high altitude are major , independent determinants of the prevalence of AMS ( 2 ) . Acute mountain sickness is not a prerequisite for HAPE . Acetazolamide ( 3 , 4 ) or dexamethasone ( 5 , 6 ) prophylaxis can prevent AMS , whereas nifedipine prophylaxis can prevent HAPE ( 7 ) . Whether acetazolamide or dexamethasone also prevents HAPE has not been studied . Exaggerated hypoxic pulmonary vasoconstriction leading to elevated pulmonary capillary pressure ( 8) is the major pathophysiologic mechanism of HAPE . This elevated pulmonary capillary pressure may be caused by inhomogeneous hypoxic pulmonary vasoconstriction ( 9 ) , which leads to areas that are subjected to high pressure and flow , consequent mechanical overdistention of pulmonary capillaries , and injury of the bloodgas barrier ( 10 ) . This phenomenon causes extravasation of fluid , plasma proteins , and blood cells into the interstitial and alveolar spaces ( 11 ) . Decreased bioavailability of nitric oxide might explain the elevated pulmonary artery pressure ( 12 , 13 ) . Therefore , phosphodiesterase-5 inhibitors are an attractive option to restore impaired effects of nitric oxide in persons susceptible to HAPE ( 1416 ) . Constitutively impaired sodium and water transport in the lung has been thought to be an additional factor in the pathogenesis of HAPE ( 17 , 18 ) . Hypoxia also decreases water reabsorption from the alveolar space . Direct experimental evidence has been obtained from hypoxia-exposed rats ( 19 ) , and indirect evidence derives from decreased sodium transport activity in cultured alveolar epithelial cells ( 20 ) . Prophylactic inhalation of the 2-adrenergic agonist salmeterol to stimulate alveolar sodium transport ( 17 ) decreased the incidence of HAPE in susceptible persons . However , other mechanisms of action may also contribute to the preventive effects of salmeterol , because -adrenergics tighten the endothelial barrier and decrease pulmonary artery pressure ( 21 ) . Dexamethasone may be an alternative therapy to prevent HAPE because it stimulates alveolar sodium and water reabsorption ( 22 ) ; may enhance nitric oxide availability in pulmonary vessels ( 23 , 24 ) ; and is effective against AMS ( 5 , 6 ) , which may develop despite use of nifedipine as prophylaxis against HAPE ( 25 ) . However , HAPE has occurred in persons who received dexamethasone for AMS ( 26 , 27 ) . We sought to test whether prophylaxis with dexamethasone or tadalafil reduces the risk for HAPE in adults with a history of HAPE on rapid ascent to 4559 m. Methods Sample and Setting Mountaineers with a history of HAPE were recruited through announcements in the journals of the Swiss Alpine Club and the German Alpine Club . Four women and 25 men with at least 1 documented episode of HAPE participated after providing written informed consent . Table 1 shows the age and average number of HAPE episodes for each participant . No participant spent more than 4 nights above 2500 m within 30 days before ascent to the Capanna Regina Margherita , Italy ( altitude , 4559 m ) . Table 1 . Participant Characteristics Two to 4 weeks before the study at the Capanna Regina Margherita , baseline evaluations were performed in Zrich , Switzerl and ( altitude , 490 m ) . For ascent , participants traveled to Alagna , Italy ( altitude , 1100 m ) , ascended to 3200 m by cable car , and continued by foot to the Capanna Gnifetti ( altitude , 3600 m ) , where they spent 1 night . The journey from the cable car arrival station ( 3200 m ) to the Capanna Gnifetti took about 1.5 hours . The next morning , the participants continued to the Capanna Regina Margherita ( about 4 hours ) , where they spent 2 nights . Figure 1 shows the study design . The institutional ethics boards of the University Hospital Zrich and University Hospital Heidelberg approved the study and its protocol , which was consistent with the principles of the Declaration of Helsinki . Figure 1 . Flow diagram of the study . Twenty-nine participants were recruited and underwent prealtitude tests , after which they were r and omly assigned to treatment groups . * Two participants in the tadalafil group were withdrawn from the study early because they required treatment for severe acute mountain sickness ( AMS ) with oxygen and dexamethasone before the first night at 4559 m , but high-altitude pulmonary edema ( HAPE ) was not diagnosed at the time of withdrawal . However , the duration of exposure to 4559 m may not have been long enough to develop HAPE . R and omization and Interventions Medication consisted of white gelatin capsules , identical in appearance , containing placebo ; tadalafil , 10 mg ( Cialis [ Eli Lilly , Geneva , Switzerl and ] ) ; or dexamethasone , 8 mg ( Fortecortin [ Merck , Dietikon , Switzerl and ] ) . Before the study , the pharmacist at the University Hospital Zrich packaged the medication into numbered bottles , which were assigned to individual participants according to a computer-generated list . R and omization was stratified by the number of previous episodes of HAPE ( 1 or 2 ) without blocking . Participants started taking the medication twice daily on the morning of the day before ascent to high altitude and continued intake until the end of the study . Primary End Point and Assessment of HAPE and AMS The primary end point was development of HAPE , which was assessed by clinical examination and chest radiography in each participant after the first and second nights at 4559 m or when HAPE or severe AMS occurred ( Figure 1 ) . Two physicians who were blinded to treatment assignment performed clinical examinations according to a predefined checklist in the mornings after the first and second night at 4559 m or when severe AMS or HAPE occurred . High-altitude pulmonary edema was clinical ly suspected at the appearance of dry cough , orthopnea , or pulmonary rales in at least 1 lung area . A posteroanterior thorax radiograph was then obtained by using a mobile unit ( TRS [ Siemens , Stockholm , Sweden ] ) at a fixed distance of 1.4 m at 95 kV and a charge of 3 to 6 mAs . Radiographs were scored retrospectively by a second radiologist who was blinded to other study results . After the lung was divided into 4 quadrants , the following scores were assigned : 1 for a question able infiltrate , 2 for interstitial edema in less than 50 % of the quadrant area , 3 for interstitial edema on 50 % or more of the quadrant area , and 4 for alveolar edema . A radiograph showing interstitial or alveolar edema ( score > 1 ) in at least 1 quadrant ( 28 ) confirmed the diagnosis of HAPE . The severity of AMS was evaluated by clinical examination and was quantified by using the Lake Louise scoring protocol ( 29 ) . Each participant answered the first 5 questions of the protocol that asked about the severity of headache , gastrointestinal symptoms , fatigue , lightheadedness or dizziness , and insomnia . A score of 0 to 3 points ( 0 = no symptoms , 1 = mild symptoms , 2 = moderate symptoms , and 3 = severe symptoms ) was assigned for each item . In clinical examination , a score of 0 ( normal ) to 4 points was given for mental status ( for which 4 points indicated coma ) and ataxia ( for which 4 points indicated inability to st and on the heel-to-toe walking test ) . A score of 1 was given for peripheral edema in 1 location , and a score of 2 was given for edema in more than 1 location . The sum of all points yielded the Lake Louise score ( maximum score , 25 points ) . A Lake Louise score greater than 4 defined AMS ( 30 ) . To assess possible side effects of the study medications , we separately evaluated the Lake Louise score question that asked for information on headache severity and the degree of insomnia , and we measured blood glucose levels in addition to vital signs . To test for adherence , participants were requested to document medication intake and investigators counted the remaining capsules at each visit . Blood and urine sample s were collected to measure cortisol and tadalafil , respectively . Treatment of HAPE and AMS consisted of nifedipine for HAPE , dexamethasone for AMS , and supplemental oxygen for both disorders . Participants who required treatment were withdrawn from the study . Echocardiography and Measurement of Cardiac Output Doppler echocardiography was performed by using an integrated color Doppler system with a 4.0-MHz transducer ( Aplio 80 [ Toshiba-Medical Systems , Oetwil am See , Switzerl and ] ) while participants were lying in a semi-supine , left-lateral position . Systolic pulmonary artery pressure was calculated from the pressure gradient across the tricuspid valve and measured with continuous-wave Doppler echocardiography by using the modified Bernoulli equation and an estimated right atrial pressure of 7 mm Hg ( 8) . Color flow imaging was used for alignment . The recordings were stored on magneto-optical disk for evaluation by 2 investigators who were blinded to all other data . Averages of at least 3 cardiac cycles were used . Cardiac output was measured by using beat-to-beat stroke volume measurement with impedance cardiography ( Task Force Monitor [ CNSystems , Graz , Austria ] ) . Nasal Potential Measurements Analgesic drugs like acetylsalicylic acid , paracetamol , and ibuprofen are frequently used by subjects suffering from headache of acute mountain sickness ( AMS ) . It is not clear if the effect is due to analgesia or prevention of AMS . We performed a r and omized controlled clinical trial comparing a low dose of an acetylsalicylic acid analog , calcium carbasalate ( 380 mg /day ) , to placebo in a cohort of altitude-naïve subjects attempting a fast climb of Mt. Kilimanjaro ( 5896 m ) . A third noncontrolled open arm was proposed-the usual recommended preventive treatment of acetazolamide 500 mg/day . Of 93 potential participants , 44 chose prevention with acetazolamide , 18 refused participation , 15 received calcium carbasalate , and 16 received placebo . Mean age was 39 + /- 9 ( SD ) yr and 15 % were female . AMS was quantified by the Lake Louise Symptom Score and physician assessment . Calcium carbasalate at 380 mg/day did not have any preventive effect on AMS and did not have any effect on the prevalence and intensity of headache . Event rate of AMS in the pooled carbasalate-placebo group was 84 % and 55 % in the acetazolamide group . The number needed to treat ( NNT ) at 500 mg/day of acetazolamide was 3 . One subject on acetazolamide developed high altitude cerebral edema and was treated with dexamethasone , oxygen , and descent by evacuation . In conclusion , low-dose calcium carbasalate is not effective for prevention of AMS . In addition , these results corroborate the contention that in typical steep climbing profile setting s , such as used by commercial enterprise on Mt. Kilimanjaro , acetazolamide 500 mg/day may not be sufficient to prevent AMS or to sufficiently reduce symptom intensity in almost half of subjects OBJECTIVE To investigate the therapeutic effect of low-concentration of nitroic oxide ( NO ) inhalation in high-altitude pulmonary edema . METHOD Sixty-five male patients with high-altitude pulmonary edema were r and omized into three groups . Patients in the conventional therapy group received oxygen , intravenous furosemide , aminophylline and dexamethasone ; patients in the nifedipine group received oral nifedipine ( 10 mg , tid ) in addition to conventional therapy ; and patients in the NO group received NO ( 10 ppm ) inhalation for 30 min , in addition to oral nifedipine . The time for which pulmonary rales on auscultation and shadows on chest radiograph lasted , and the course of disease , were compared . RESULT In the NO group , pulmonary rales disappeared in 0.4 + /- 0.3 d , shadows on chest radiograph disappeared in 0.6 + /- 0.2 d , and the course of disease was 1.8 + /- 0.7 d , all of which were significantly different from those of the nifedipine group ( 2.4 + /- 1.4 d , 4.1 + /- 1.7 d , 6.8 + /- 1.8 d , respectively ) and the conventional therapy group ( 3.7 + /- 1.2 d , 5.5 + /- 1.8 d , 9.6 + /- 3.1 d , respectively ) . CONCLUSION Low-concentration NO inhalation on the basis of conventional and nifedipine therapies was very effective in the treatment of high-altitude pulmonary edema , which deserves further and larger scale investigation “ Live High-Train Low ” ( LHTL ) training can alter oxidative status of athletes . This study compared prooxidant/antioxidant balance responses following two LHTL protocol s of the same duration and at the same living altitude of 2250 m in either normobaric ( NH ) or hypobaric ( HH ) hypoxia . Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocol s in a cross-over and r and omized manner : Living altitude ( PIO2 = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH , respectively ) ; training “ natural ” altitude ( ~1000–1100 m ) and training loads were precisely matched between both LHTL protocol s. Plasma levels of oxidative stress [ advanced oxidation protein products ( AOPP ) and nitrotyrosine ] and antioxidant markers [ ferric-reducing antioxidant power ( FRAP ) , superoxide dismutase ( SOD ) and catalase ] , NO metabolism end-products ( NOx ) and uric acid ( UA ) were determined before ( Pre ) and after ( Post ) the LHTL . Cumulative hypoxic exposure was lower during the NH ( 229 ± 6 hrs . ) compared to the HH ( 310 ± 4 hrs . ; P<0.01 ) protocol . Following the LHTL , the concentration of AOPP decreased ( -27 % ; P<0.01 ) and nitrotyrosine increased ( + 67 % ; P<0.05 ) in HH only . FRAP was decreased ( -27 % ; P<0.05 ) after the NH while was SOD and UA were only increased following the HH ( SOD : + 54 % ; P<0.01 and UA : + 15 % ; P<0.01 ) . Catalase activity was increased in the NH only ( + 20 % ; P<0.05 ) . These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes . Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH In this r and omized , double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema ( HAPE ) in trekkers traveling between 4250 m (Pheriche)\4350 m ( Dingboche ) and 5000 m ( Lobuje ) in Nepal ; to determine if acetazolamide decreases pulmonary artery systolic pressures ( PASP ) at high altitude ; and to determine if there is an association with PASP and signs and symptoms of HAPE . Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje . The Lake Louise Consensus Criteria were used for the diagnosis of HAPE , and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP . Complete measurements were performed on 339 of the 364 subjects ( 164 in the placebo group , 175 in the acetazolamide group ) . No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups . Mean PASP values did not differ significantly between the acetazolamide and placebo groups ( 31.3 and 32.6 mmHg , respectively ) . An increasing number of signs and symptoms of HAPE was associated with elevated PASP ( p < 0.01 ) . The efficacy of acetazolamide against acute mountain sickness , however , was significant with a 21.9 % incidence in the placebo group compared to 10.2 % in the acetazolamide group ( p < 0.01 ) . Given the lack of cases of HAPE in either group , we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE , but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 Background — The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1 . The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension , renal water , and sodium balance under acute and prolonged exposure to high-altitude – associated hypoxia . Methods and Results — In a double-blind fashion , healthy volunteers were r and omly assigned to receive bosentan ( 62.5 mg for 1 day and 125 mg for the following 2 days ; n=10 ) or placebo ( n=10 ) at sea level and after rapid ascent to high altitude ( 4559 m ) . At sea level , bosentan did not induce any significant changes in hemodynamic or renal parameters . At altitude , bosentan induced a significant reduction of systolic pulmonary artery pressure ( 21±7 versus 31±7 mm Hg , P<0.03 ) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment . However , both urinary volume and free water clearance ( H2OCl/glomerular filtration rate ) were significantly reduced versus placebo after 2 days of ET-1 antagonism ( 1100±200 versus 1610±590 mL ; −6.7±3.5 versus −1.8±4.8 mL/min , P<0.05 versus placebo for both ) . Sodium clearance and segmental tubular function were not significantly affected by bosentan administration . Conclusions — The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation . These findings must be considered for the prevention and treatment of acute mountain sickness Bloch , Konrad E. , Alex and er J. Turk , Marco Maggiorini , Thomas Hess , Tobias Merz , Martina M. Bosch , Daniel Barthelmes , Urs Hefti , Jacqueline Pichler , Oliver Senn , and Otto D. Schoch . Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata , 7546 m. High Alt . Med . Biol . 10:25 - 32 , 2009.- Data on acclimatization during expedition-style climbing to > 5000 m are scant . We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness ( AMS ) symptoms and mountaineering success in climbers to Muztagh Ata ( 7546 m ) , Western China . We performed a r and omized , controlled trial during a high altitude medical research expedition to Muztagh Ata . Thirty-four healthy mountaineers ( mean age 45 yr , 7 women ) were r and omized to follow one of two protocol s , ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m , respectively . The main outcome measures , AMS symptom scores and the number of proceeding climbers , were assessed daily . Mean + /- SD AMS-C scores of 16 climbers r and omized to slow ascent were 0.06 + /- 0.18 , 0.26 + /- 0.08 , 0.41 + /- 0.45 , 0.53 + /- 0.77 at camps I ( 5533 m ) , II ( 6265 m ) , III ( 6865 m ) , and the summit ( 7546 m ) , respectively . Corresponding values in 18 climbers r and omized to fast ascent were significantly higher : 0.17 + /- 0.23 , 0.43 + /- 0.75 , 0.49 + /- 0.36 , and 0.69 + /- 0.54 ( p < 0.008 , vs. slow ascent in regression analysis accounting for weather-related protocol deviation ) . Climbers r and omized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers r and omized to fast ascent ( p = 0.04 , Kaplan-Meier analysis ) . More climbers r and omized to slow ascent were successful in reaching the highest camp at 6865 m without AMS ( odds ratio 9.5 ; 95 % confidence interval 1.02 to 89 ) . In climbers ascending to very high altitudes , differences of a few days in acclimatization have a significant impact on symptom severity , the prevalence of AMS , and mountaineering success . Clinical Trials.gov Identifier NCT00603122 Background — This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice . Methods and Results — In a r and omized , double-blind study , sildenafil 100 mg or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11 % O2 for 30 minutes . Pulmonary artery pressure ( PAP ) was measured with an indwelling right heart catheter . The acute 56 % increase in mean PAP produced by hypoxia during placebo treatment ( mean PAP [ mean±SD mm Hg ] : normoxia 16.0±2.1 versus hypoxia 25.0±4.8 ) was almost abolished by sildenafil ( normoxia 16.0±2.1 versus hypoxia 18.0±3.6 ) , with no significant effect on systemic blood pressure . In the isolated perfused lung of wild-type and endothelial nitric oxide synthase (eNOS)-deficient mice , sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction . Wild-type mice dosed orally with the drug ( 25 mg · kg−1 · d−1 ) throughout 3 weeks of exposure to hypoxia ( 10 % O2 ) exhibited a significant reduction in right ventricular systolic pressure ( placebo versus sildenafil : 43.3±9.9 versus 29.9±9.7 mm Hg , P < 0.05 ) coupled with a small reduction in right ventricular hypertrophy and inhibition of pulmonary vascular remodeling . In eNOS mutant mice , sildenafil attenuated the increase in right ventricular systolic pressure but without a significant effect on right ventricular hypertrophy or vascular remodeling . Conclusions — Sildenafil attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a novel approach to the treatment of this condition . The eNOS-NO-cGMP pathway contributes to the response to sildenafil , but other biochemical sources of cGMP also play a role . Sildenafil has beneficial pulmonary hemodynamic effects even when eNOS activity is impaired High-altitude tourism is increasingly frequent , involving also subjects with manifest or sub clinical coronary artery disease . Little is known , however , on the effects of altitude exposure on factors affecting coronary perfusion . The aim of our study was to assess myocardial oxygen supply/dem and ratio in healthy subjects during acute exposure at high altitude and to evaluate the effect of acetazolamide on this parameter . Forty-four subjects ( 21 men , age range : 24–59 years ) were r and omized to double-blind acetazolamide 250 mg bid or placebo . Subendocardial viability ratio and oxygen supply/dem and ratio were estimated on carotid artery by means of a vali date d PulsePen tonometer , at sea level , before and after treatment , and after acute and more prolonged exposure to high altitude ( 4559 m ) . On arrival at high altitude , subendocardial viability ratio was reduced in both placebo ( from 1.63±0.15 to 1.18±0.17 ; P<0.001 ) and acetazolamide ( from 1.68±0.25 to 1.35±0.18 ; P<0.001 ) groups . Subendocardial viability ratio returned to sea level values ( 1.65±0.24 ) after 3 days at high altitude under acetazolamide but remained lower than at sea level under placebo ( 1.42±0.22 ; P<0.005 versus baseline ) . At high altitude , oxygen supply/dem and ratio fell both under placebo ( from 29.6±4.0 to 17.3±3.0 ; P<0.001 ) and acetazolamide ( from 32.1±7.0 to 22.3±4.6 ; P<0.001 ) , its values remaining always higher ( P<0.001 ) on acetazolamide . Administration of acetazolamide may , thus , antagonize the reduction in subendocardial oxygen supply triggered by exposure to hypobaric hypoxia . Further studies involving also subjects with known or sub clinical coronary artery disease are needed to confirm a protective action of acetazolamide on myocardial viability under high-altitude exposure Abstract Observations on acute mountain sickness occurring between 11,000 and 18,000 feet , in 1925 men , 18 , to 53 years old , showed no direct relation between altitude and severity of illness ; mild , moderate and severe cases occurred at all altitudes . A time lag of six to 96 hours between arrival and onset of symptoms ruled out any direct relation between hypoxia and acute mountain sickness . During this period there was clinical evidence of respiratory dysfunction with slow , irregular or Cheyne — Stokes breathing , pulmonary congestion and antidiuresis . In one biopsy and two autopsy studies there was evidence of cerebral edema . Diuresis induced with furosemide provided effective routine therapy . Morphine and betamethasone were used as additional aids in severe cases . Clinical features of acute mountain sickness were ascribed to hypoxia , pulmonary congestion , increased cerebral blood flow , increased cerebrospinal-fluid pressure and cerebral edema 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 There is an expectation that repeated daily exposures to normobaric hypoxia ( NH ) will induce ventilatory acclimatization and lessen acute mountain sickness ( AMS ) and the exercise performance decrement during subsequent hypobaric hypoxia ( HH ) exposure . However , this notion has not been tested objective ly . Healthy , unacclimatized sea-level ( SL ) residents slept for 7.5 h each night for 7 consecutive nights in hypoxia rooms under NH [ n = 14 , 24 ± 5 ( SD ) yr ] or " sham " ( n = 9 , 25 ± 6 yr ) conditions . The ambient percent O(2 ) for the NH group was progressively reduced by 0.3 % [ 150 m equivalent ( equiv ) ] each night from 16.2 % ( 2,200 m equiv ) on night 1 to 14.4 % ( 3,100 m equiv ) on night 7 , while that for the ventilatory- and exercise-matched sham group remained at 20.9 % . Beginning at 25 h after sham or NH treatment , all subjects ascended and lived for 5 days at HH ( 4,300 m ) . End-tidal Pco(2 ) , O(2 ) saturation ( Sa(O(2 ) ) ) , AMS , and heart rate were measured repeatedly during daytime rest , sleep , or exercise ( 11.3-km treadmill time trial ) . From pre- to posttreatment at SL , resting end-tidal Pco(2 ) decreased ( P < 0.01 ) for the NH ( from 39 ± 3 to 35 ± 3 mmHg ) , but not for the sham ( from 39 ± 2 to 38 ± 3 mmHg ) , group . Throughout HH , only sleep Sa(O(2 ) ) was higher ( 80 ± 1 vs. 76 ± 1 % , P < 0.05 ) and only AMS upon awakening was lower ( 0.34 ± 0.12 vs. 0.83 ± 0.14 , P < 0.02 ) in the NH than the sham group ; no other between-group rest , sleep , or exercise differences were observed at HH . These results indicate that the ventilatory acclimatization induced by NH sleep was primarily expressed during HH sleep . Under HH conditions , the higher sleep Sa(O(2 ) ) may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise performance for the remainder of each day 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 a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Acetazolamide treatment ameliorates the symptoms of AMS ; however , the mechanism by which this occurs is unclear . To examine the effects of acetazolamide on oxygenation , CO2 responsiveness and ventilatory pattern during acute exposure to HA , we studied two groups of subjects at SL and following rapid ( less than 8 h ) transport to HA . Acetazolamide or placebo tablets were given to groups 1 and 2 , respectively , in a double-blind manner after baseline SL measurements ; treatment was continued during HA exposure . There was no difference in the ventilatory pattern at HA , between the two groups . While the Ve achieved in response to CO2 at HA vs SL was much greater in each group the percent change from baseline at HA versus that at SL was not significantly different . The beneficial effects of acetazolamide in AMS are associated with a higher level of ventilation at HA and better oxygenation : CO2 chemosensitivity is not affected by acetazolamide at HA Acute mountain sickness ( A.M.S. ) and its severe complications , high-altitude pulmonary oedema ( H.A.P.O. ) and cerebral oedema ( C.O. ) , were studied in 278 unacclimatised hikers at 4243 m altitude at Pheriche in the Himalayas of Nepal . The overall incidence of A.M.S. was 53 % , the incidence being increased in the young and in those who flew to 2800 m , climbed fast , and spent fewer nights acclimatising en route . It was unrelated to sex , to previous altitude experience , to the load carried , and to recent respiratory infections . The severity of A.M.S. was inversely related to age ( independent of rate of ascent ) and the highest altitude attained , and was highly ocrrelated with speed of ascent . There were 7 cases of H.A.P.O. and 5 with the more intractable C.O. and , of these 12 , 11 had flown in , 9 had spent only one night at Pheriche , and none were on acetazolamide . 11 required evacuation . Acetazolamide , compared in a double-blind study with a placebo and also compared with no tablets at all , reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude . Prevention consists in slow ascent , rapid recognition of warning signs , and prompt descent to avoid progression BACKGROUND Acute mountain sickness ( AMS ) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis ; however , there is conflicting evidence regarding the efficacy of Ginkgo biloba use . We performed a r and omized , placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis . METHODS We r and omized unacclimatized adults to receive acetazolamide , Ginkgo biloba , or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours . We grade d AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System ( LLS ) and compared the incidence of AMS ( defined as LLS score > or =3 and headache ) . RESULTS Fifty-seven subjects completed the trial ( 20 received acetazolamide ; 17 , Ginkgo biloba , and 20 , placebo ) . The LLS scores were significantly different between groups ; the median score of the acetazolamide group was significantly lower than that of the placebo group ( P=.01 ; effect size , 2 ; and 95 % confidence interval [ CI ] , 0 to 3 ) , unlike that of the Ginkgo biloba group ( P=.89 ; effect size , 0 ; and 95 % CI , -2 to 2 ) . Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group ( effect size , 30 % ; 95 % CI , 61 % to -15 % ) , and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group ( effect size , -5 % ; 95 % CI , -37 % to 28 % ) . CONCLUSIONS In this study , prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence . We found no evidence of similar efficacy for Ginkgo biloba Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness ( AMS ) . Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS . To determine whether lower , less frequent doses were effective in preventing AMS , 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber on two occasions while taking one of three doses of dexamethasone ( 4 mg , 1 mg , or .25 mg every 12 h ) or a placebo in a double-blind , crossover design . The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels . Dexamethasone did not alter fluid balance or plasma volume changes , but treatment with 1 mg and 4 mg suppressed cortisol secretion . There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment . The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS , while lower doses are relatively ineffective At altitudes of 3000 - 5000 m about 20 - 50 % of skiers and mountaineers experience headache , the main symptom of acute mountain sickness.1 Although most mountaineers know that they should avoid climbing great heights too early on and too fast , they may not always act accordingly . The use of drugs to prevent and treat headaches at high altitudes is therefore widespread , aspirin being one of the most commonly taken . We tested the efficacy of aspirin as prophylaxis against headache at high altitudes . Twenty nine volunteers with a history of headache at high altitude were r and omly assigned in a double blind fashion to receive placebo ( eight men , six women , mean age 38 ( SD 12 ) years ) or 320 mg aspirin ( nine men , six women , mean age 38 ( 14 ) years ) . After examination at low altitude ( 600 m ) , subjects were transported to high altitude ( 3480 m ) The pathophysiology of acute mountain sickness ( AMS ) is unknown . One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier ( BBB ) and , subsequently , lead to the development of cerebral edema and the defining symptoms of AMS . This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption . Twenty healthy volunteers participated in a series of hypobaric hypoxia trials distinguished by pretreatment with placebo , acetazolamide ( 250 mg ) , or dexamethasone ( 4 mg ) , administered using a r and omized , double-blind , placebo-controlled , crossover design . Each trial included peripheral blood sampling and AMS assessment before ( -15 and 0 h ) and during ( 0.5 , 4 , and 9 h ) a 10-h hypoxic exposure ( barometric pressure = 425 mmHg ) . Anti-inflammatory and /or anti-permeability [ interleukin (IL)-1 receptor agonist ( IL-1RA ) , heat shock protein (HSP)-70 , and adrenomedullin ] , proinflammatory ( IL-6 , IL-8 , IL-2 , IL-1β , and substance P ) , angiogenic , or chemotactic biomarkers ( macrophage inflammatory protein-1β , VEGF , TNF-α , monocyte chemotactic protein-1 , and matrix metalloproteinase-9 ) were assessed . AMS-resistant subjects had higher IL-1RA ( 4 and 9 h and overall ) , HSP-70 ( 0 h and overall ) , and adrenomedullin ( overall ) compared with AMS-susceptible subjects . Acetazolamide raised IL-1RA and HSP-70 compared with placebo in AMS-susceptible subjects . Dexamethasone also increased HSP-70 and adrenomedullin in AMS-susceptible subjects . Macrophage inflammatory protein-1β was higher in AMS-susceptible than AMS-resistant subjects after 4 h of hypoxia ; dexamethasone minimized this difference . Other biomarkers were unrelated to AMS . Resistance to AMS was accompanied by a marked anti-inflammatory and /or anti-permeability response that may have prevented downstream pathophysiological events leading to AMS . Conversely , AMS susceptibility does not appear to be related to an exaggerated inflammatory response Previous attempts to detect global cerebral hemodynamic differences between those who develop headache , nausea , and fatigue following rapid exposure to hypoxia [ acute mountain sickness ( AMS ) ] and those who remain healthy have been inconclusive . In this study , we investigated the effects of two drugs known to reduce symptoms of AMS to determine if a common cerebral hemodynamic mechanism could explain the prophylactic effect within individuals . With the use of r and omized , placebo-controlled , double-blind , crossover design , 20 healthy volunteers were given oral acetazolamide ( 250 mg ) , dexamethasone ( 4 mg ) , or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4,875 m in a hypobaric chamber , which included 2 h of exercise at 50 % of altitude-specific VO(2max ) . Cerebral hemodynamic parameters derived from ultrasound assessment s of dynamic cerebral autoregulation and vasomotor reactivity were recorded 15 h prior to and after 9 h of hypoxia . AMS symptoms were scored using the Lake Louise Question naire ( LLQ ) . It was found that both drugs prevented AMS in those who became ill on placebo ( ~70 % decrease in LLQ ) , yet a common cerebral hemodynamic mechanism was not identified . Compared with placebo , acetazolamide reduced middle cerebral artery blood flow velocity ( 11 % ) and improved dynamic cerebral autoregulation after 9 h of hypoxia , but these effects appeared independent of AMS . Dexamethasone had no measureable cerebral hemodynamic effects in hypoxia . In conclusion , global cerebral hemodynamic changes result ing from hypoxia may not explain the development of AMS The effect of acetazolamide ( Az ) on exercise performance and muscle mass in acclimatised subjects at an altitude of 4846 m was assessed in 11 subjects and compared with the effect of placebo on 10 other subjects . Exercise performance at 85 % maximum heart rate fell by 37 % in the Az group and by 45 % in controls ( p less than 0.05 ) . Weight loss was greater in the placebo group at high altitude ( p less than 0.01 ) and this correlated with the fall in exercise performance ( p less than 0.001 ) . During the expedition anterior quadriceps muscle thickness fell by 12.9 % in the control group and 8.5 % in the Az group ( p less than 0.001 ) , while biceps muscle thickness fell by 8.6 % in controls and 2.3 % in the Az group ( p less than 0.001 ) . Measurements of skin-fold thickness indicated a loss of 18 % of total body fat in the placebo group and 5 % in the Az group by the end of the expedition ( p less than 0.001 ) . Calorie intakes at altitudes above 3000 m were low and similar for the two groups . The Az group had fewer symptoms of acute mountain sickness but differences between the two groups were not statistically significant . Acetazolamide is therefore useful for climbers and trekkers who are acclimatised to high altitudes . It could be most useful at extreme altitudes , where maintenance of exercise performance and muscle mass are important OBJECTIVE Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions . The mechanisms accounting for this sex-related difference are not completely understood . Acetazolamide effectively counteracts nocturnal periodic breathing , but it has been investigated almost exclusively in men . Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women . We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women , and that acetazolamide , by leftward shifting the CO2 ventilatory response , could improve nocturnal periodic breathing at altitude in a sex-independent manner . METHODS Forty-four healthy lowl and ers ( 21 women ) , r and omized to acetazolamide or placebo , underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude . Hypoxic and hypercapnic chemosensitivities were assessed at sea level . RESULTS Men , more frequently than women , exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude . Acetazolamide leftward shifted the CO2 set point and , at altitude , improved oxygenation and reduced periodic breathing in both sexes , but to a larger extent in men . Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group . CONCLUSIONS The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity . Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes , modifying the apneic threshold and improving oxygenation . TRIAL REGISTRY EU Clinical Trials Register , EudraCT ; No. : 2010 - 019986 - 27 ; URL : https://www . clinical trialsregister.eu Previous research has demonstrated that blood and urine concentrations of various leukotrienes are elevated with acute hypoxic exposure . Some of these studies have suggested that leukotrienes may be mediators in the pathogenesis of acute mountain sickness ( AMS ) . We conducted a r and omized , double-blind study to determine if AMS symptoms correlated with the increase in leukotriene synthesis and if prophylactic leukotriene receptor blockade would prevent the development of AMS in a simulated high altitude exposure . Three male and five female subjects completed two normobaric hypoxia chamber exposures ( average F(IO2 ) 12.4 + /- 0.09 % ) , receiving montelukast 10 mg daily for 4 days prior to one session and placebo for 4 days prior to the other session . There were no differences in Lake Louise AMS scores , time spent in the chamber , average oxygen saturation , and average heart rate during the montelukast and placebo sessions . Headache scores were higher during treatment with montelukast than during treatment with placebo . Compared to preexposure values , urinary leukotriene E4 concentrations were unchanged during the hypoxic chamber exposure following treatment with placebo or montelukast . Urinary leukotriene E4 excretion during the hypoxic exposure did not differ between the two sessions . A 4-day course of leukotriene receptor blockade does not prevent symptoms of AMS . These results suggest that leukotrienes do not play a causal role in the pathophysiology of AMS Blood pressure increases during acute exposure to high altitude in healthy humans . However , little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition . Objectives of High Altitude Cardiovascular Research (HIGHCARE)– And es Lowl and ers Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting . One hundred untreated subjects with mild hypertension ( screening blood pressure , 144.1±9.8 mm Hg systolic , 92.0±7.5 mm Hg diastolic ) were r and omized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination . Twenty-four – hour ambulatory blood pressure monitoring was performed off-treatment , after 6 weeks of treatment at sea level , on treatment during acute exposure to high altitude ( 3260 m ) and immediately after return to sea level . Eighty-nine patients completed the study ( age , 56.4±17.6 years ; 52 men/37 women ; body mass index , 28.2±3.5 kg/m2 ) . Twenty-four – hour systolic blood pressure increased at high altitude in both groups ( placebo , 11.0±9 mm Hg ; P<0.001 and active treatment , 8.1±10.4 mm Hg ; P<0.001 ) . Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude ( 147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated ; P<0.001 ; 95 % confidence interval of the difference 10.9–19.9 mm Hg ) and was well tolerated . Similar results were obtained for diastolic , for daytime blood pressure , and for nighttime blood pressure . Treatment was well tolerated in all conditions . Our study demonstrates that ( 1 ) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and ( 2 ) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01830530 BACKGROUND Oral glucocorticoids can prevent acute mountain sickness ( AMS ) . Whether inhaled budesonide ( BUD ) can prevent AMS remains unknown . OBJECTIVE Our aim was to investigate the effectiveness of BUD in AMS prevention . METHODS Eighty subjects were r and omly assigned to receive budesonide ( BUD , inhaled ) , procaterol tablet ( PT ) , budesonide/formoterol ( BUD/FM , inhaled ) , or placebo tablet ( n = 20 in each group ) . Subjects were treated for 3 days before ascending from 500 m to 3700 m within 2.5 h by air . Lake Louis AMS question naire , blood pressure , heart rate , and oxygen saturation ( SpO2 ) were examined at 20 , 72 , and 120 h after high-altitude exposure . Pulmonary function was measured at 20 h after exposure . RESULTS Compared with placebo , BUD significantly reduced the incidence of AMS ( 70 % vs. 25 % at 20 h , p < 0.05 ; both 10 % vs. 5 % at 72 and 120 h , both p > 0.05 ) without side effects . The relative risk was 0.357 , and the risk difference was 0.45 . Mean SpO2 was higher in BUD , BUD/FM , and PT groups than in the placebo group at 20 h ( p < 0.05 ) . SpO2 in all 80 subjects dropped after ascent ( 98.1 % to 88.12 % , p < 0.01 ) and increased gradually , but it was still lower at 120 h than at baseline ( 92.04 % vs. 98.1 % , p < 0.01 ) . Pulmonary function did not differ among the four groups at 20 h. CONCLUSION BUD can prevent AMS without side effects . The alleviation of AMS may be related to increased blood oxygen levels rather than pulmonary function BACKGROUND Acute Mountain Sickness ( AMS ) is a multi-system disorder that is characterized by headache , anorexia , nausea , vomiting , insomnia , lassitude , and malaise . The syndrome is common in unacclimatized low altitude residents who rapidly ascend to terrestrial elevations exceeding 2,500 m. AMS may be a manifestation of hypoxia-induced cerebral edema result ing , in part , from increased capillary permeability . HYPOTHESIS We hypothesized that cysteinyl leukotrienes ( CysLTs ) may be involved in the pathogenesis of AMS , as these compounds are known to increase endothelial permeability . METHODS To test this hypothesis , we orally administered a CysLTs type-1 receptor antagonist ( montelukast ) to 11 subjects prior to and during exposure to high altitude ( 4,300 m ) in a hypobaric chamber in a r and omized , placebo-controlled , crossover design . We measured the result ing prevalence and /or severity of AMS , plasma CysLTs levels and urinary CysLTE4 , and associated physiological responses . RESULTS At 12 h exposure , AMS prevalence and symptom severity was lower ( p = 0.002 ) during montelukast administration compared with placebo , but not different at 22 h exposure . Plasma CysLTs and urinary LTE4 levels were not significantly elevated at 22 h exposure , nor did these CysLTs levels correlate with AMS severity . Compared with placebo , montelukast administration was not associated with any significant differences in physiologic measures at sea level or high altitude . CONCLUSIONS These results do not support a role for the CysLTs mediating the early development of AMS through the CysLT-1 receptor To test the value of dexamethasone acetate for ameliorating acute mountain sickness ( AMS ) , we conducted a double-blind , r and omized study that compared the effects of 4 mg of dexamethasone acetate or a placebo ( given every six hours for six doses beginning at the time of exposure ) at 2700 and 2050 m. Study subjects , who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains , were classified as having AMS when they reported three or more of the five usual symptoms ( headache , insomnia , dyspnea , anorexia , and /or fatigue ) on a single day . All symptoms with an intensity of at least grade 2 ( moderate ) out of 5 were analyzed . At 2700 m , there was a 50 % decrease in the mean AMS symptom score in the dexamethasone group ( 0.94 + /- 1.11 vs 1.84 + /- 1.44 [ mean + /- SD ] ) and the incidence of AMS was 20 % of that in the control group ( 3/38 vs 14/35 ) . At 2050 m , there was no difference between dexamethasone and a placebo in the mean AMS symptom score ( 1.52 + /- 1.50 vs 1.24 + /- 1.33 ) and the incidence of AMS ( 5/25 vs 4/25 ) . Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 A controlled comparative between-group study of 48 climbers ascending Kilimanjaro ( 5895 m ) was design ed as an extension to our previous double-blind cross-over trial on the same peak in 1980 , using acetazolamide to decrease the incidence and effects of Acute Mountain Sickness . A group taking acetazolamide 500 mg each morning for one day befare reaching 3000 m were compared with 3 control groups of Caucasian subjects and lowl and and highl and Africans . Efficacy was assessed on climbing performance and scores derived from symptoms recorded daily by subjects . Those taking acetazolamide reached higher altitudes and had lower symptom scores than those in control groups . The results support the use of acetazolamide as an effective prophylactic for Acute Mountain Sickness , for most people in a dose of 500 mg in the morning starting one day before ascent above 3000 m . The optimal dose of prophylactic acetazolamide is not established , nor is the most appropiate time for medication prior to ascent Abstract Objective To evaluate the efficacy of ginkgo biloba , acetazolamide , and their combination as prophylaxis against acute mountain sickness . Design Prospect i ve , double blind , r and omised , placebo controlled trial . Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002 . Participants 614 healthy western trekkers ( 487 completed the trial ) assigned to receive ginkgo , acetazolamide , combined acetazolamide and ginkgo , or placebo , initially taking at least three or four doses before continued ascent . Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom . Secondary outcome measures included blood oxygen content , severity of syndrome ( Lake Louise scores ≥ 5 ) , incidence of headache , and severity of headache . Results Ginkgo was not significantly different from placebo for any outcome ; however participants in the acetazolamide group showed significant levels of protection . The incidence of acute mountain sickness was 34 % for placebo , 12 % for acetazolamide ( odds ratio 3.76 , 95 % confidence interval 1.91 to 7.39 , number needed to treat 4 ) , 35 % for ginkgo ( 0.95 , 0.56 to 1.62 ) , and 14 % for combined ginkgo and acetazolamide ( 3.04 , 1.62 to 5.69 ) . The proportion of patients with increased severity of acute mountain sickness was 18 % for placebo , 3 % for acetazoalmide ( 6.46 , 2.15 to 19.40 , number needed to treat 7 ) , 18 % for ginkgo ( 1 , 0.52 to 1.90 ) , and 7 % for combined ginkgo and acetazolamide ( 2.95 , 1.30 to 6.70 ) . Conclusions When compared with placebo , ginkgo is not effective at preventing acute mountain sickness . Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness Cerebral edema occurs in fatal cases of acute mountain sickness . Dexamethasone , commonly used to treat cerebral edema due to other causes , also reduces the symptoms of acute mountain sickness when given prophylactically . However , the efficacy of dexamethasone in the treatment of established acute mountain sickness remains uncertain . To investigate this question , we exposed six men in a hypobaric chamber to a simulated altitude of 3700 m ( barometric pressure , 64 kPa [ 481 mm Hg ] ) for 48 hours on two occasions . Acute mountain sickness was diagnosed with use of a symptoms question naire , and dexamethasone ( 4 mg every six hours ) or placebo was then given in a r and omized , double-blind , crossover fashion . Dexamethasone reduced the symptoms of acute mountain sickness by 63 percent ( P less than 0.05 ) , whereas placebo had a minimal effect ( reduction by 23 percent ; P not significant ) . In spite of this response , one subject had mild cerebral edema on brain CT after both placebo and dexamethasone . Dexamethasone had no effect on fluid shifts , oxygenation , sleep apnea , urinary catecholamine levels , the appearance of chest radiographs or perfusion scans , serum electrolyte levels , hematologic profiles , or the results of psychometric tests . Dexamethasone treatment was complicated by mild hyperglycemia in all subjects ( mean [ + /- SE ] glucose level , 7.3 + /- 1.3 mmol per liter [ 132 + /- 23 mg per deciliter ] ) . We conclude that dexamethasone effectively reduces the symptoms of acute mountain sickness . However , it did not improve objective physiologic abnormalities related to exposure to high altitudes . We therefore recommend that dexamethasone be used only when descent is impossible , or to facilitate cooperation in evacuation efforts In a r and omized , double-blind cross-over study 10 subjects were exposed to a simulated altitude of 4500 m for 10 h after administration of placebo , acetozolamide ( 250 mg bid ) or theophylline ( 250 mg bid ) . T2-weighted magnetic resonances images ( MRI ) and diffusion weighted MRI were obtained directly after exposure to altitude under hypoxic conditions . Although eight of 10 subjects had moderate to severe acute mountain sickness ( AMS ) , we found no evidence of cerebral oedema , irrespective of the medication taken . Almost all subjects showed a decrease in inner cerebrospinal fluid ( iCSF ) volumes ( placebo −10.3 % , P = 0.02 ; acetazolamide −13.2 % , P = 0.008 , theophylline −12.2 % , n.s . ) . There was no correlation between AMS symptoms and fluid shift . However , we found a significantly positive correlation of large ( > 10 ml ) iCSF volume and more severe AMS after administration of placebo ( r = 0.76 , P = 0.01 ) . Moderate to severe AMS after high altitude exposure for 10 h is associated with a decreased iCSF-volume independent of AMS severity or medication without signs of cerebral oedema Up to half of those who ascend rapidly to altitudes of over 3,000 m may experience symptoms of acute mountain sickness ( AMS ) and of these some 95 % may suffer from high altitude headache . We report the first controlled trial specifically to assess an oral drug therapy for this common symptom . Subjects were 21 members of mountaineering expeditions to similar altitudes in the Bolivian And es and the Himalayas in Nepal . The study was of a r and omized , placebo-controlled , double-blind , within-patient crossover design . Ibuprofen was significantly superior to placebo both in reducing headache severity and in speed of relief ( a mean difference of 94 min in time to no/minimal headache ) . Only 14 % of subjects who initially took ibuprofen felt the need for further medication compared to 83 % of those who took placebo first ( p = 0.02 ) . Of the 11 subjects completing both phases of the crossover , 8 ( 73 % ) favored ibuprofen while the remainder had no preference ( p = 0.004 ) . No attributable adverse effects occurred . The results suggest that ibuprofen is a safe and effective treatment for high altitude headache Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness ( AMS ) . Evidence suggests that they may also reduce pulmonary artery systolic pressure ( PASP ) . To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude , a r and omized controlled trial was conducted on 28 healthy young men with acetazolamide ( 125 mg bid ) , gingko biloba ( 120 mg bid ) , or placebo for 3 days prior to airlift ascent ( 397 m ) and for the first 3 days at high altitude ( 3658 m ) . PASP , AMS , arterial oxygen saturation ( Sao2 ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , forced vital capacity ( FVC ) , forced expiratory volume in the first second ( FEV1 ) , and peak expiratory flow ( PEF ) were assessed both at 397 m and 3658 m. HR , PEF , and PASP increased with altitude exposure ( p<0.05 ) , and SaO2 decreased ( p<0.05 ) . PASP with acetazolamide ( mean at 3658 m , 26.2 mm Hg ; incremental change , 4.7 mm Hg , 95 % CI . , 2.6 - 6.9 mm Hg ) was lower than that with ginkgo biloba ( mean at 3658 m , 33.7 mm Hg , p=0.001 ; incremental change , 13.1 mm Hg , 95%CI . , 9.6 - 16.5 mm Hg , p=0.002 ) , and with placebo ( mean at 3658 m , 34.7 mm Hg , p<0.001 ; 14.4 mm Hg , 95 % CI . , 8.8 - 20.0 mm Hg , p=0.001 ) . The data show that a low prophylactic dosage of acetazolamide , but not gingko biloba , mitigates the early increase of PASP in a quick ascent profile A r and omized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes > 2,500 m. Fourteen healthy male subjects participated in a r and omized single-blind placebo-controlled crossover study carried out in a decompression chamber ( simulated altitude 4,500 m ) . A second r and omized single-blind , placebo-controlled study was conducted at a high-altitude research laboratory ( 3,454 m ) and included 21 healthy male subjects . The study medication was either 375 mg oral slow-release theophylline ( 250 mg if < 70 kg ) or a matched placebo tablet taken twice daily . The acute mountain sickness score ( AMSS ) was assessed three times a day , beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure . In addition , measurements of respiratory frequency , pulse rate , oxygen saturation and arterial blood gas levels were performed . Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study ( mean+/-SD 1.2+/-0.9 ) with placebo versus 3.6+/-0.8 with theophylline ; p=0.03 ) . During the high-altitude study , subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude ( 0.6 versus 2.3 , p=0.03 ) . Oxygenation was improved in both parts of the study . In conclusion , oral slow-release theophylline improves acute mountain sickness The objective of this study was to determine the efficacy of low-dose acetazolamide ( 125 mg twice daily ) for the prevention of acute mountain sickness ( AMS ) . The design was a prospect i ve , double-blind , r and omized , placebo-controlled trial in the Mt. Everest region of Nepal between Pheriche ( 4243 m ) , the study enrollment site , and Lobuje ( 4937 m ) , the study endpoint . The participants were 197 healthy male and female trekkers of diverse background , and they were evaluated with the Lake Louise Acute Mountain Sickness Scoring System and pulse oximetry . The main outcome measures were incidence and severity of AMS as judged by the Lake Louise Question naire score at Lobuje . Of the 197 participants enrolled , 155 returned their data sheets at Lobuje . In the treatment group there was a statistically significant reduction in incidence of AMS ( placebo group , 24.7 % , 20 out of 81 subjects ; acetazolamide group , 12.2 % , 9 out of 74 subjects ) . Prophylaxis with acetazolamide conferred a 50.6 % relative risk reduction , and the number needed to treat in order to prevent one instance of AMS was 8 . Of those with AMS , 30 % in the placebo group ( 6 of 20 ) versus 0 % in the acetazolamide group ( 0 of 9 ) experienced a more severe degree of AMS as defined by a Lake Louise Question naire score of 5 or greater ( p = 0.14 ) . Secondary outcome measures associated with statistically significant findings favoring the treatment group included decrease in headache and a greater increase in final oxygen saturation at Lobuje . We concluded that acetazolamide 125 mg twice daily was effective in decreasing the incidence of AMS in this Himalayan trekking population The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness ( AMS ) at moderate altitude in ambulatory travelers not undergoing vigorous exercise . Volunteers vacationing in La Paz , Bolivia ( 3630 m ) , immediately after arrival from sea level were studied . The design was a double-blind , r and omized trial of two doses of acetazolamide ( 125 mg twice daily , 250 mg twice daily ) versus placebo twice daily over a 24-h period . The main outcome measure was AMS score and score trend , using the Lake Louise consensus question naire . Nine of 32 subjects ( 28 % ) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h ( respectively ) , the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo , 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose , and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose . The absolute change in these mean scores was not significant for placebo ( p = 0.21 ) or the 125-mg dose ( p = 0.88 ) , but was significant for the 250-mg dose ( p = 0.008 ) . A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo ( p = 0.002 ) . The 250-mg dose of acetazolamide twice daily ( but not 125 mg twice daily ) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily RATIONALE Acute mountain sickness ( AMS ) may affect individuals who ( rapidly ) ascend to altitudes higher than 2,000 - 3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema , a hydrostatic edema associated with increased pulmonary capillary pressures . Acetazolamide is effective against AMS , possibly by increasing ventilation and cerebral blood flow ( CBF ) . In animals , it inhibits hypoxic pulmonary vasoconstriction . OBJECTIVES We examined the influence of acetazolamide on the response to hypoxia of ventilation , CBF , and pulmonary vascular resistance ( PVR ) . METHODS In this double-blind , placebo-controlled , r and omized study , nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day , we measured the responses of ventilation , PVR , and CBF to acute isocapnic hypoxia ( 20 min ) and sustained poikilocapnic hypoxia ( 4 h ) . Ventilation was measured with pneumotachography . Hypoxia was achieved with dynamic end-tidal forcing . The maximum pressure difference across the tricuspid valve ( DeltaPmax , a good index of PVR ) was measured with Doppler echocardiography . CBF was measured by transcranial Doppler ultrasound . RESULTS In normoxia , acetazolamide increased ventilation and reduced DeltaPmax , but did not influence CBF . The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered , but the rise in DeltaPmax was reduced by 57 % . The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34 % after acetazolamide , the ventilatory response was increased , but the CBF response remained unaltered . CONCLUSIONS Acetazolamide has complex effects on ventilation , PVR , and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema Acetazolamide ( ACZ ) is used to prevent acute mountain sickness at altitude . Because it could affect O2 transport in several different and potentially conflicting ways , we examined its effects on pulmonary and muscle gas exchange and acid-base status during cycle exercise at approximately 30 , 50 and 90 % VO2max in normoxia ( F(IO2 ) = 0.2093 ) and acute hypoxia ( F(IO2 ) = 0.125 ) . In a double-blind , order-balanced , crossover design , six healthy , trained men ( normoxic VO2max= 59 ml kg(-1 ) min(-1 ) ) exercised at both F(IO2 ) values after ACZ ( 3 doses of 250 mg , 8 h apart ) and placebo . One week later this protocol was repeated using the other drug ( placebo or ACZ ) . We measured cardiac output ( QT ) , leg blood flow ( LBF ) , and muscle and pulmonary gas exchange , the latter using the multiple inert gas elimination technique . ACZ did not significantly affect VO2 , QT , LBF or muscle gas exchange . As expected , ACZ led to lower arterial and venous blood [ HCO3- ] , pH and lactate levels ( P < 0.05 ) , and increased ventilation ( P < 0.05 ) . In both normoxia and hypoxia , ACZ result ed in higher arterial P(O2 ) and saturation and a lower alveolar-arterial P(O2 ) difference ( AaD(O2 ) ) due to both less VA/Q mismatch and less diffusion limitation ( P < 0.05 ) . In summary , ACZ improved arterial oxygenation during exercise , due to both greater ventilation and more efficient pulmonary gas exchange . However , muscle gas exchange was unaffected OBJECTIVE To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude , alone and in conjunction with acetazolamide , and to assess the effect on acute mountain sickness ( AMS ) . DESIGN Two placebo-controlled trials during rapid ascent to high altitude . PARTICIPANTS In the first trial , 20 participants , and in the second trial , 24 participants . SETTING During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION In the first trial , participants were r and omized to receive medroxyprogesterone 30 mg or a placebo twice a day . In the second trial , participants were r and omly assigned to one of 4 groups : a placebo twice daily , medroxyprogesterone 30 mg twice daily , acetazolamide 250 mg plus a placebo twice daily , or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily . MAIN OUTCOME MEASURES Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only . RESULTS Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide . Cerebral regional oxygen saturation was not altered by medroxyprogesterone . The reduction in symptom scores and in the extent of AMS was not significant in this limited study . CONCLUSIONS Medroxyprogesterone acts as a respiratory stimulant , but the clinical benefit regarding the development of AMS was unproven at high altitude . Combined medroxyprogesterone and acetazolamide gave the best PaO2 Nifedipine has been shown effective for prevention and treatment of high altitude pulmonary edema ( HAPE ) . Because acute mountain sickness ( AMS ) and HAPE may share common pathophysiologic mechanisms , we evaluate the prophylactic effect of nifedipine on the development of AMS in 27 mountaineers not susceptible to HAPE . They were r and omly assigned to receive in a double-blind manner either nifedipine or placebo during rapid ascent to 4559 m and a subsequent three-day sojourn at this altitude . Nine of 14 subjects on nifedipine and eight of 13 subjects on placebo felt ill at high altitude . Pulmonary artery pressures ( PAP ) estimated by Doppler echocardiography were significantly lower with nifedipine , but arterial PO2 , oxygen saturation , and alveolar-arterial oxygen pressure gradient were not significantly different between groups at high altitude . This study demonstrates that lowering PAP has no beneficial effect on gas exchange and symptoms of AMS in subjects not susceptible to HAPE . Therefore , nifedipine can not be recommended for prevention of AMS , and its use in high altitude medicine should be limited to prevention and treatment of HAPE We wished to determine in a field study the effectiveness of dexamethasone for prevention and treatment of acute mountain sickness ( AMS ) . Prevention Trial : We transported 15 subjects from sea level to 4,400 m ( PB = 400 mm Hg ) on Denali ( Mt. McKinley ) by means of a 1-h helicopter flight . In a r and omized , double-blind fashion we gave eight subjects a placebo and seven subjects 2 mg dexamethasone orally every 6 h , starting 1 h before take-off . The entire placebo group and five of the dexamethasone group developed AMS within 5 h , and became progressively more ill until 12 h when the trial was terminated . We concluded that 2 mg of dexamethasone every 6 h did not prevent AMS in active soldiers rapidly transported to high altitude . Treatment Trial : We treated 11 of those with moderate to severe AMS ( symptom score 4.5 + /- 0.7 , range 3 to 11 ) with 4 mg of dexamethasone every 6 h orally or intramuscularly for 24 h. All were markedly improved at 12 h ( symptom score 1.0 + /- 0.3 , p less than 0.001 , range 0 to 3 ) , but symptoms increased after the drug was discontinued at 24 h ( symptom score = 2.4 + /- 0.5 ) . We conclude that dexamethasone in a dosage of 4 mg PO or IM every 6 h is an effective treatment for AMS , but that illness may recur with abrupt discontinuation of the drug Previous studies have shown low-dose acetazolamide to be effective in preventing AMS in persons already at high altitude and then moving higher , a relatively low risk situation . We wished to evaluate prophylactic administration of low-dose acetazolamide for reducing the incidence and severity of AMS in a high-risk setting : rapid ascent from 1600 to 4300 m. We performed a double-blind , r and omized , placebo-controlled study with human subjects ( n=44 ) exposed to 4300 m for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during day 1 at altitude with placebo ( n=22 ) or acetazolamide 250 mg/day ( 125 mg bid , n=22 ) . AMS diagnosis required both an AMS-C score from the Environmental Symptom Question naire-III > or=0.7 and a Lake Louise Symptom ( LLS ) question naire score > or=3 plus headache . Acetazolamide reduced the incidence of AMS compared to placebo-treated subjects ( 14 % vs. 45 % , respectively , p=0.02 ) , and the number needed to treat was 3 . The AMS-C and LLS scores were lower in acetazolamide-treated subjects , indicating less severe AMS . Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting Objective Acute mountain sickness ( AMS ) characterized by presence of symptoms including headache , nausea , excessive fatigue , loss of appetite , irritability and insomnia is a major impediment to work performance in human subjects who are rapidly inducted to high altitude ( HA ) during the initial phase of induction . The present study aims at to evaluate the efficacy of prophylactic administration of low dose glucocorticoids in prevention of AMS in normal healthy men who are inducted to HA by air STUDY OBJECTIVES To compare the benefits of simulated descent in a hyperbaric chamber with those of supplementary oxygen for the treatment of acute mountain sickness . DESIGN A prospect i ve study . SETTING The Snake River Health Clinic in Keystone , Colorado , which has an altitude of 2,850 m ( 9,300 ft ) . TYPE OF PARTICIPANTS Twenty-four patients who presented with acute mountain sickness . INTERVENTIONS A simulated descent of 1,432 m ( 4,600 ft ) was attained by placing the patients in a fabric hyperbaric chamber and pressurizing the chamber to 120 mm Hg ( 2.3 PSI ) above ambient pressure . Patients were r and omly assigned to either the hyperbaric treatment or treatment with 4 L of oxygen given by facemask ; both treatments lasted for two hours . MEASUREMENTS AND MAIN RESULTS Mean arterial oxygen saturation ( SaO2 ) increased 7 % ( 84 + /- 2 % to 91 + /- 1 % ) with pressurization and 14 % ( 83 + /- 4 % to 96 + /- 1 % ) with oxygen during treatment over pretreatment levels . Symptoms of acute mountain sickness decreased as rapidly with pressurization as with oxygen treatment , despite significantly higher SaO2 in the oxygen-treated group during treatment . Symptomatic improvement was retained in both groups at least one hour after treatment . CONCLUSION Simulated descent in a fabric hyperbaric chamber is as effective as oxygen therapy for the immediate relief of acute mountain sickness Abstract Objective .—This study aim ed to determine the efficacy , tolerability , and practicality of acetazolamide for the prevention of acute mountain sickness ( AMS ) in Nepali trekking porters early in the trekking season . Methods .—This study was a r and omized , double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal , trekking from Namche Bazaar ( 3440 m ) to Lobuche ( 4930 m ) , the study endpoint . Participants were r and omized to receive 250 mg acetazolamide daily or placebo , and AMS symptom scores ( Lake Louise ) were compared in highl and ers vs lowl and ers . Results .—Only 109 ( 27.2 % ) of the 400 porters completed the trial ( 28 highl and ers , 81 lowl and ers ) . The rest either dropped out ( 275/400 porters , 68.8 % ) or were excluded ( 16/400 porters , 4 % ) . Acute mountain sickness occurred in 13 ( 11.9 % ) of 109 porters ; all were lowl and ers ; 7 were taking acetazolamide , 6 taking placebo . Birthplace , acclimatization in the week before the trial , ascent rate , and rest days were the most important variables affecting the incidence of AMS . No highl and ers , but 13 ( 16.1 % ) of 81 lowl and ers had AMS ( P = .016 ) . Acclimatization in the pretrial week reduced AMS incidence ( P = .013 ) , as did a slower ascent rate ( P = .0126 ) , but rest days were the most potent prophylactic variable ( P = .0001 ) . Side effects were more frequent in porters taking acetazolamide than in the placebo group ( P = .0001 ) , but there were no serious side effects . Conclusions .—Acetazolamide was tolerable , but impractical for the routine prevention of AMS in Nepali porters . A good trekking schedule and adequate acclimatization remain the most effective preventive measures . This study identified lowl and porters as a high-risk group for developing AMS Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness ( AMS ) during gradual ascent . This trial was design ed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent . In this double-blind , r and omized , placebo-controlled trial , 26 participants residing at sea level received ginkgo ( 60 mg TID ) or placebo starting 24 h before ascending Mauna Kea , Hawaii . Subjects were transported from sea level to the summit ( 4205 m ) over 3 hours , including 1 hour at 2835 m. The Lake Louise Self-report Question naire constituted the primary outcome measure at baseline , 2835 m , and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score ( LLSR ) > /= 3 with headache . Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study . The ginkgo ( n = 12 ) and placebo ( n = 14 ) groups were well matched ( 58 % vs. 50 % female ; median age 28 yr , range 22 - 53 vs. 33 yr , range 21 - 53 ; 58 % vs. 57 % Caucasian ) . Two ( 17 % ) subjects on ginkgo and nine ( 64 % ) on placebo developed severe AMS and required descent for their safety ( p = 0.021 ) ; all recovered without sequelae . Median LLSR at 4205 m was significantly lower for ginkgo versus placebo ( 4 , range 1 - 8 vs. 5 , range 2 - 9 , p = 0.03 ) . Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo ( ginkgo 7/12 , 58.3 % vs. placebo 13/14 , 92.9 % , p = 0.07 ) . Twenty-one of 26 ( 81 % ) subjects developed AMS overall . This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 High altitude pulmonary edema ( HAPE ) is characterized by marked pulmonary hypertension . Treatment of 6 subjects suffering from radiographically documented HAPE with the calcium channel blocker nifedipine , lowered pulmonary artery pressure and result ed in clinical improvement , better oxygenation , reduction of alveolar-arterial oxygen gradient and a progressive clearing of alveolar edema on chest x-ray . This amelioration occurred despite continued exercise at an altitude above 4000 m and without supplementary oxygen . Prophylactic application of nifedipine slow release preparation , 20 mg every 8 hours , prevented HAPE in 9 out of 10 subjects with a history of radiographically documented HAPE upon rapid ascent and subsequent stay to an altitude of 4559 m. Seven of 11 comparable subjects who received placebo developed pulmonary edema at 4559 m. As compared with the subjects who received placebo , those who received nifedipine had a significantly lower mean systolic pulmonary artery pressure , alveolar-arterial pressure gradient of oxygen and symptom score of acute mountain sickness at 4559 m. Thus nifedipine offers a potential emergency treatment of HAPE when descent or evacuation is impossible and oxygen is not available . Prophylactic administration of nifedipine prevents HAPE in susceptible subjects . High pulmonary artery pressure has an important role in the pathogenesis of HAPE Abstract The influence of acetazolamide on acute mountain sickness was tested in a double-blind study of forty-three volunteers given acetazolamide or placebo , 250 mg every eight hours , for 32 hours before and 40 hours after abrupt transportation from sea level to 12,800 feet . In response to hypoxia , control subjects hyperventilated and developed mild respiratory alkalosis with increased blood pH and reduced carbon dioxide tension and bicarbonate within eight hours after arrival at altitude . These changes persisted over the five days of the study . Alkalosis was prevented in the acetazolamide-treated group , with a greater increase in ventilation and alveolar oxygen tension and a greater decrease in carbon dioxide tension and bicarbonate than in controls . Significant reductions in frequency and severity of the most prominent symptoms of acute mountain sickness — headache , insomnia and gastrointestinal symptoms — were observed in treated subjects . In control subjects , occurrence and severity of symptoms corr In a previous controlled study , dexamethasone ( DEX ) was shown to prevent acute mountain sickness ( AMS ) during exposure to simulated high altitude . To determine the effect of DEX during actual altitude exposure , 16 young men were treated with either DEX ( 4 mg every 6 h ) or placebo for 48 h prior to and 48 h after being rapidly transported from sea level to the summit of Pikes Peak , CO ( 4,300 m ) . Symptoms of AMS were evaluated twice daily at Pikes Peak using the Environmental Symptoms Question naire and a clinical assessment . During treatment the mean symptom scores were higher for subjects taking placebo in 18 out of 20 comparisons . On an individual basis , 60 % of the subjects receiving placebo met the criteria for being " sick " compared to 31 % of subjects receiving DEX . Beginning 24 h after cessation of treatment , DEX subjects experienced a progressive increase in symptom scores which lasted through the end of the altitude sojourn ( day 6 ) . The results indicate that DEX is an effective prophylactic treatment for AMS in an actual mountain environment , but that AMS symptoms can occur if the drug is stopped abruptly The study assessed physiological responses to induction to high altitude first to 3,500 m and then to 4,200 m and compared the time course of altitude acclimatization in two groups of male volunteers . The acutely inducted group was transported by aircraft ( AI ) to 3,500 m in 1 h , whereas the gradually inducted group was transported by road ( RI ) in 4 days . Baseline recordings of basal cardiovascular , respiratory , and blood gas variables were monitored at sea level as well as at 3,500 m on days 1 , 3 , 5 , and 7 . Blood gases were measured on day 10 also . After 15 days at 3,500 m , the subjects were inducted to 4,200 m by road , and measurements were repeated on days 1 , 3 , and 5 , except blood gas variables , which were done on day 10 only . Acute mountain sickness symptoms were recorded throughout . The responses of RI were stable by day 3 of induction at 3,500 m , whereas it took 5 days for AI . Four days in transit for RI appear equivalent to 2 days at 3,500 m for AI . Acclimatization schedules of 3 and 5 days , respectively , for RI and AI are essential to avoid malacclimatization and /or high-altitude illness . Both groups took 3 days at 4,200 m to attain stability for achieving acclimatization OBJECTIVE Headache , nausea , and sleeplessness at altitude [ acute mountain sickness ( AMS ) ] are major health problems for several million mountain recreationists who ascend to high altitudes each year . We aim ed to test the efficacy of low-dose , slow-release theophylline for the prevention of AMS in a placebo-controlled , double-blind , r and omized trial . METHODS Twenty healthy male volunteers ( mean age 34.7 y ) were r and omized ( r and om allocation ) to receive either 300 mg theophylline daily or placebo 5 days prior , during ascent , and during a stay at 4,559 m altitude . AMS symptoms were collected using the Lake Louise Score on each day during ascent and at high altitude . A 12-channel sleep recorder recorded sleep and breathing parameters during the first night at 4,559 m. Theophylline serum levels were drawn prior to the sleep study . RESULTS Seventeen completed the entire study . Theophylline ( n = 9 ) compared to placebo ( n = 8) significantly reduced AMS symptoms at 4,559 m ( Lake Louise Score : 1.5 + /- 0.5 vs placebo 2.3 + /- 2.37 ; p < 0.001 ) , events of periodic breathing ( 34.3/h vs placebo 74.2/h ; p < 0.05 ) , and oxygen desaturations ( 62.3/h vs placebo 121.6/h ; p < 0.01 ) . No significant differences in sleep efficiency or sleep structure were present in the two groups . No adverse drug effects were reported . CONCLUSIONS Low-dose , slow-release theophylline reduces symptoms of AMS in association with alleviation of events of periodic breathing and oxygen desaturations We r and omly assigned 32 healthy backpackers to receive placebo , acetazolamide ( 250 mg twice a day ) , dexamethasone acetate ( 4 mg four times a day ) , or both drugs in combination to determine the drug efficacy in preventing acute mountain sickness ( AMS ) at altitudes of 3,650 to 4,050 m ( 12,000 to 13,300 ft ) . The incidence of AMS was high but symptoms were generally mild . Combined drug therapy was superior to both placebo and single drug therapy in risk reduction . Using acetazolamide alone was moderately beneficial in preventing the occurrence of AMS , although minor side effects were frequent . The use of dexamethasone alone did not significantly reduce the AMS incidence , and discontinuing its use result ed in symptoms suggestive of adrenal insufficiency . For recreational backpackers , routine drug prophylaxis is not recommended , in view of the mild nature of this illness and the adverse effects of medications . The efficacy of combined acetazolamide-dexamethasone therapy warrants further investigation at higher altitudes , where AMS is more severe , and the dexamethasone should be withdrawn gradually to avoid a possible adrenal crisis Forty-seven climbers participated in a double-blind , r and omized trial comparing acetazolamide 250 mg , dexamethasone 4 mg , and placebo every eight hours as prophylaxis for acute mountain sickness during rapid , active ascent of Mount Rainier ( elevation 4,392 m ) . Forty-two subjects ( 89.4 percent ) achieved the summit in an average of 34.5 hours after leaving sea level . At the summit or high point attained above base camp , the group taking dexamethasone reported less headache , tiredness , dizziness , nausea , clumsiness , and a greater sense of feeling refreshed ( p less than or equal to 0.05 ) . In addition , they reported fewer problems of runny nose and feeling cold , symptoms unrelated to acute mountain sickness . The acetazolamide group differed significantly ( p less than or equal to 0.05 ) from other groups at low elevations ( 1,300 to 1,600 m ) , in that they experienced more feelings of nausea and tiredness , and they were less refreshed . These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness . Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone . This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease Context A few small retrospective studies show associations between obesity and acute mountain sickness . Contribution This 24-hour study involving 9 obese and 10 nonobese men was conducted in a decompression chamber that simulated a rapid ascent to an altitude of 3658 m ( 12 000 ft ) . Obese men more often developed symptoms of mountain sickness and had lower nocturnal oxygen saturation values than did nonobese men . Caution s Although this elegant , short experiment suggests that obese men were more susceptible to acute mountain sickness , the study involved few people , simulated a steady rate of ascent , and did not simulate physical activity with altitude exposure . The Editors Rapid ascent from low to high altitude ( above 2500 m or 8200 ft ) often causes acute mountain sickness ( AMS ) , a syndrome characterized by headache and other systemic symptoms , such as nausea , lassitude , and difficulty sleeping . The prevalence and severity of AMS depend on the speed of ascent , the altitude attained , preacclimatization , age , sex , exertion levels while at altitude , and the ventilatory response to acute hypoxia ( 1 , 2 ) . Few retrospective field studies of high altitude have reported that obesity , as evidence d by body mass index ( BMI ) , might be associated with the development of AMS ( 3 - 7 ) . However , this association has not been studied prospect ively under controlled conditions at reasonably accessible altitudes or in individuals with mild to moderate obesity . We sought to determine whether obese individuals are more likely to develop AMS than nonobese individuals during decompression to a simulated altitude of 3658 m. We hypothesized that obese individuals were more susceptible to develop AMS than nonobese individuals during exposure to high altitudeinduced hypobaric hypoxia . Methods Participants Volunteers were recruited through local advertisements and were selected for participation on the basis of percentage body fat . Nonobese was defined as percentage body fat less than 25 % . Obese was defined as a BMI of 30 kg/m2 or greater and percentage body fat of 30 % or greater . None of the participants had a history of cardiovascular or respiratory abnormalities . No participant was taking long-term medications . All participants were nonsmokers . Nine obese men ( mean age [ SD ] , 35 8 years ) and 10 nonobese men ( mean age [ SD ] , 34 8 years ) were studied . All participants resided at sea level ( 100 m ) in Dallas , Texas . One obese and three nonobese participants previously had mild AMS . One obese participant was exposed to a 2500-m altitude 4 days before this study ; no other participant was exposed to a 1500-m or higher altitude before participating in the study . Each participant received both written and verbal explanations of the experiment before giving written consent . The Institutional Review Board of the University of Texas Southwestern Medical Center and Presbyterian Hospital of Dallas approved this study . Study Protocol The study was conducted in a large ( 40 ft long by 9 ft diameter ) multiplace ( room for > 1 person ) decompression chamber at the Institute for Exercise and Environmental Medicine in Dallas . The barometric pressure was held at 483 mm Hg , which is equivalent to an altitude of 3658 m ( 12 000 ft ) . The temperature ( 25 0.5 C ) , humidity ( 28 % 1 % ) , and concentration of CO2 ( 0.07 % 0.02 % ) in the chamber were monitored continuously by trained medical staff . Four participants at a time were studied in the chamber during the 24 hours of exposure ( Figure 3 ) . Assessment of AMS According to guidelines established by the Lake Louise AMS consensus report ( 8) , each participant completed an AMS self-report question naire at sea level ( before decompression ) and during decompression to 483 mm Hg at 6 hours , 12 hours , and 24 hours . The question naire included items for symptoms of headache , gastrointestinal symptoms , fatigue or weakness , dizziness or lightheadedness , and difficulty sleeping . Each symptom was grade d on a scale from 0 to 3 , with 0 representing no symptoms ; 1 , mild symptoms ; 2 , moderate symptoms ; and 3 , severe symptoms . A score of 15 was the maximum score possible . A self-score of 4 or more was an indication of AMS ( 8) . This scoring system has been vali date d against the U.S. Army Environmental Symptoms Question naire , demonstrating similar sensitivity and specificity ( 9 ) . Measurements of Sao 2 Daytime Sao 2 was measured by pulse oximetry ( Ohmeda 3700 Pulse Oximeter , Date x-Ohmeda , Boulder , Colorado ) at sea level and at 6 hours and 24 hours of simulated altitude . Nocturnal Sao 2 in each participant was continuously recorded in the chamber from 10:30 p.m. to 6:30 a.m. The mean nocturnal Sao 2 was calculated from values obtained every 30 minutes . Heart rate was measured at sea level and at altitude during the daytime and during sleep . Other Measurements Body composition was determined by hydrostatic weighing , and percentage body fat , fat mass , and lean mass were calculated . At sea level , all participants underwent st and ard spirometry ( measuring lung volumes , maximal flow-volume loop , and maximal voluntary ventilation ) and diffusing capacity of the lung in a whole-body plethysmograph ( Model 6200 , SensorMedics , Yorba Linda , California ) . Pulmonary function testing was performed according to the guidelines of the American Thoracic Society . Statistical Analysis Data are expressed as means ( SD ) . The parameters of AMS score and Sao 2 were analyzed by a two-way analysis of variance ( ANOVA ) using SAS software , release 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) , with repeated measures on one factor ( altitude-time ) and between-participant comparisons for the other factor ( group , nonobese and obese ) . Comparisons were considered significant when the P value was less than 0.05 . Role of the Funding Sources The funding sources had no role in the design , conduct , or reporting of the study or in the decision to su bmi t the manuscript for publication . Results Participants The Table shows general characteristics of the participants . One participant in the obese group was removed from the chamber after 10 hours because of severe headache , nausea , and dizziness ( AMS score , 8) . As a result , this participant was not included in further analyses . Table . General Characteristics and Pulmonary Function of Participants at Baseline AMS Scores There was a significant interaction between altitude-time and group ( P < 0.001 ) as a result of the two-way ANOVA . This indicated that the increase in AMS scores with altitude exposure was more pronounced in the obese participants ( Figure 1 ) . Overall , after 24 hours in the chamber , seven obese participants and four nonobese participants had an AMS score of 4 or more . The frequency of AMS symptoms at 24 hours in 18 participants was as follows : headache , 89 % ; gastrointestinal upset , 36 % ; fatigue and weakness , 36 % ; dizziness , 15 % ; and difficulty sleeping , 75 % . Figure 1 . Comparison of the acute mountain sickness ( AMS ) score at sea level and at simulated altitude for 24 hours in nonobese ( n = 10 ) and obese ( n = 8) participants . P Sao 2 There was also a significant interaction between altitude-time and group ( P < 0.001 ) for Sao 2 as a result of the two-way ANOVA ( Figure 2 ) . This indicated that the decrease in Sao 2 with altitude exposure differed between the two groups . Figure 2 . Comparison of Sao at sea level , during the daytime , and during sleep at night in nonobese ( n = 10 ) and obese ( n = 8) participants . o P Figure 3 . Participants during simulated altitude exposure in decompression chamber . Discussion Our principal finding was that obese participants have higher AMS scores than nonobese participants during a 24-hour exposure to simulated altitude of 3658 m. Thus , obesity seems to be associated with the development of AMS . Also , the response of Sao 2 with exposure differed between nonobese and obese men ; obese men had lower values than nonobese men . These findings suggest that impaired breathing during sleep may be an important pathophysiologic mechanism for the increased levels of AMS in obese individuals . Limitations Although our results suggest that obese individuals may be more susceptible to AMS , these results must be interpreted with caution . Possible limitations to generalization include the small sample size , the selected nature of the study sample , the narrow spectrum of obese participants studied , the steady rate of ascent , the lack of physical activity during altitude exposure , and the simulated environment in which the participants were studied . Obesity and AMS Obesity is characterized by an abnormally large adipose tissue mass . In particular , excess weight leads to the development of various pathophysiologic disorders and , specifically , cardiovascular and respiratory abnormalities . Obesity-related respiratory function abnormalities , such as sleep-disordered breathing and nocturnal hypercapnia and hypoxia , place obese individuals at risk for illness at higher altitudes ( 10 - 13 ) . In addition , the prevalence of obesity in western society , especially in the United States ( where 22 % of the population has a BMI > 30 kg/m2 and roughly 30 % of the population is overweight [ 14 , 15 ] ) , further increases the potential for altitude-related difficulties at easily accessible high altitudes during recreational activities . A review of the literature revealed no prospect i ve data on the effect of obesity on high-altitude illness . In our study , AMS scores increased with time during altitude exposure in both nonobese and obese participants , which is consistent with previous data demonstrating that AMS symptoms are common after 24 hours of rapid ascent to high altitude ( 1 , 2 ) . The severity of symptoms , however , significantly differed between nonobese and obese men , suggesting that the occurrences of AMS at high altitude may be closely related to increased body weight . Acute mountain sickness frequently occurs in travelers who rapidly ascend to an altitude of 2500 m without acclimatizing ; the incidence and severity depend on the speed of Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions . In a r and omized , double-blind , placebo-controlled study , the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined . Twelve subjects ( sildenafil [ SIL ] n = 6 ; placebo [ PLA ] n = 6 ) were exposed for 6 days at 4,350 m. Treatment ( 3 x 40 mg/day ) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days . Systolic pulmonary artery pressure ( echocardiography ) increased at high altitude before treatment ( + 29 % versus sea level , p < 0.01 ) , then normalized in SIL ( -6 % versus sea level , NS ) and remained elevated in PLA ( + 21 % versus sea level , p < 0.05 ) . Pulmonary acceleration time decreased by 27 % in PLA versus 6 % in SIL ( p < 0.01 ) . Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups . Pa(O(2 ) ) was higher and alveolar-arterial difference in O(2 ) lower in SIL than in PLA at rest and exercise ( p < 0.05 ) . The altitude-induced decrease in maximal O(2 ) consumption was smaller in SIL than in PLA ( p < 0.05 ) . Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange , limiting the altitude-induced hypoxemia and decrease in exercise performance METHOD We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract ( EGb 761 ) on acute mountain sickness ( AMS ) and vasomotor changes of the extremities during a Himalayan expedition . After giving their written informed consent , the subjects were r and omized to two groups . One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo . Assessment was based on the course of the Environmental Symptom Question naire ( ESQ ) score and the cold gradient measured by photoplethysmography . RESULTS The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study . In terms of factor 1 ( AMS-Cerebral ) , no subject in the EGb 761 group developed acute mountain sickness versus 40.9 % of subjects in the placebo group ; this difference was very significant ( p < or = 1.4 x 10(-3 ) ) . In terms of factor 2 ( AMS-Respiratory ) , 3 subjects ( 13.6 % ) in the EGb 761 group developed acute mountain sickness versus 18 ( 81.8 % ) in the placebo group ; this difference was very significant ( p = 1.2 x 10(-5 ) ) . CONCLUSION Due to its multiple pharmacological actions , EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude ( 5400 m ) with gradual exposure . It also decreased vasomotor disorders of the extremities , as demonstrated by plethysmography ( p < 10(-8 ) ) and a specific question naire ( p < 10(-9 ) ) BACKGROUND Hypoxemia is the immediate consequence of hyobaric hypoxia , which is the crucial starting mechanism of acute mountain sickness ( AMS ) . The AMS is generally a benign and self-limiting condition which can be prevented by gradual ascent . However , ascent rates recommended for prophylaxis of AMS are far slower than those attempted during military operations and by climbers . OBJECTIVE The current study was carried out to quantify the relationship between AMS and hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone chemoprophylaxis during acute ascent . SUBJECTS AND METHODS Twenty-four low l and er male adults ( age mean + /- SE 27.8 + /- 1.24 years ) were selected . They were grouped in a double-blind fashion into four groups and each group ( n = 6 ) received placebo ( multivitamin ) or acetazolamide ( 250 mg ) or dexamethasone ( 4 mg ) or a combined regimen of the two drugs twice daily for 5 days , commencing 24 hours before ascent . The volunteers reached the altitude of 4578 meters within a span of one day . Their AMS symptoms were recorded on modified environmental symptoms question naire ( ESQ ) , after 24 and 72 hours of ascent . Arterial PO2 , SO2 and PCO2 were measured by GEMSTAT blood-gas analyzer ( Mallincrodt-USA ) . RESULTS The ESQ , AMS-C ( cerebral ) and AMS-R ( respiratory ) scores of combined therapy group were significantly lower as compared to the other groups on the symptom rating scale . The significant finding amongst the volunteers taking acetazolamide was mild to moderate diuresis whereas severity of headache was markedly less in dexamethasone group . The commonest feature of combined therapy was that none of the volunteers complained of headache , dysponea , irritability and more than mild disturbance of sleep . The ESQ scores of volunteers were inversely correlated to PaO2 and SaO2 after 24 hours of ascent to 4578 meters . CONCLUSION The study concludes that severity of AMS is closely related to hypoxemia and combination therapy of acetazolamide-dexamethasone may be effective in preventing AMS We investigated whether a diet of increased carbohydrate content reduces the symptoms of acute mountain sickness ( AMS ) and whether concentrations of circulating cytokines rise and correlate with hypoxia and AMS . There were 19 healthy volunteers who ingested in r and omized order both a high carbohydrate ( 68 % CHO ) or normal carbohydrate ( 45 % CHO ) diet for 4 d. On the 4th d , subjects were exposed to 8 h of 10 % normobaric oxygen . Each subject completed the Lake Louise Consensus Question naire ( LLCQ : a question naire developed to quantify the common symptoms and consequences of AMS ) at the beginning and end of each hypoxic session , at which times venous blood was obtained for the following cytokines : interleukins 1 beta , 6 and 8 ( IL-1 beta , IL-6 , IL-8 ) and tumor necrosis factor alpha ( TNF-alpha ) . AMS symptoms did not differ significantly between the diets ( LLCQ scores : 68 % CHO = 10.1 + /- 3.8 vs. 45 % CHO = 10.3 + /- 4.1 ) . Cytokine concentrations did not change with hypoxia on either diet , nor did individual changes correlate with AMS symptoms . We conclude that a high carbohydrate diet for 4 d does not reduce the symptoms of AMS ; and plasma cytokine concentrations do not change with hypoxia and the development of AMS and , thus , are not likely mediators of this syndrome Altitude exposure alters hemodynamics and sympathoadrenal function and elicits acute mountain sickness ( AMS ) . Since dexamethasone prevents AMS and influences responsiveness to catecholamines , we studied hemodynamic and sympathoadrenal responses to 4,570 m simulated altitude in 8 subjects treated with dexamethasone or placebo . Mean pulse rates were less at altitude with dexamethasone ( 96.1 for placebo and 84.1 for dexamethasone ; treatment-altitude interaction , p = 0.0045 ) . Altitude led to a postural decline in mean arterial pressure ( posture-altitude interaction , p = 0.0026 ) , but this was not affected by dexamethasone . Dexamethasone reduced urinary epinephrine to a greater extent during altitude exposure ( from 9.41 ng.mg-1 creatinine with placebo to 4.16 with dexamethasone ) when compared with sea level ( from 3.24 to 3.08 ) . Urinary excretion of norepinephrine was unchanged at altitude . We conclude that acute altitude exposure is associated with stimulation of the adrenal medulla and not the sympathetic nervous system . Dexamethasone blocks the adrenal medullary response and blunts the pulse rate increase at altitude OBJECTIVE To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure . METHODS Totally 100 young male army members newly recruited from Sichuan province ( 400 meters above sea level ) were enrolled . They were r and omly divided into two groups : 50 in aminophylline group ( A group ) and 50 in control group ( C group ) . A group and C group orally took aminophylline and placebo respectively for 10 days , 7 days before entering Lhasa ( 3 658 meters above sea level ) by air and 3 days after it . Several parameters were measured at three time points : before drug taken , 7 days after drug taken , and 3 days after ascending high altitude . These parameters included serum levels of nitric oxide ( NO ) , superoxide dismutase ( SOD ) , catalase ( CAT ) , hydrogen dioxide ( H2O2 ) , lactic acid ( LA ) , as well as arterial oxygen saturation ( SO2 ) , arterial oxygen partial pressure ( PaO2 ) , and arterial carbon dioxide partial pressure ( PaCO2 ) . Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system . RESULTS There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area . Three days after ascending high altitude , the serum levels of SOD , CAT , H2O2 , LA , PaCO2 increased in both groups , yet to a much larger degree in C group than A group ( P < 0.01 ) ; and NO , SO2 , PaO2 decreased more markedly in C group ( P < 0.05 for NO , P < 0.0001 for SO2 and PaO2 ) . CONCLUSION Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude The pituitary-adrenocortical and adrenomedullary response to high altitude ( HA ) stress was studied following daily single dose administration of prednisolone as a prophylaxis against altitude-induced acute mountain sickness ( AMS ) . Forty healthy men , r and omly divided into two groups of twenty , received placebo or prednisolone 20 mg once a day at 08.00 h for two days prior to induction to HA and during an initial three days stay at an altitude of 3450 m. The AMS score and circulatory levels of ACTH , cortisol , epinephrine and norepinephrine were measured at sea level ( SL ) and during residency at HA . The sensitivity of the hypothalamic-pituitary-adrenal axis in subjects receiving prednisolone therapy was evaluated at SL and on day four of stay at HA . Administration of prednisolone significantly ( p < 0.01 ) decreased the severity of AMS in all the subjects . The steroid dose used did not inhibit endogenous secretion of ACTH , cortisol , epinephrine or norepinephrine , as HA response to adrenocortical and adrenomedullary hormones was identical in placebo and prednisolone treated subjects . The integrity of the hypothalamic-pituitary-adrenal axis was maintained well in subjects receiving low dose prednisolone therapy . These observations suggest that short-term administration of prednisolone is able to curtail AMS without causing suppression of the hypothalamic-pituitary-adrenal axis 750 mg per day of acetazolamide in the prevention of acute mountain sickness ( AMS ) , as recommended in the meta- analysis published in 2000 in the British Medical Journal , may be excessive and is controversial . To determine if the efficacy of low-dose acetazolamide 125 mg bd ( 250 mg ) , as currently used in the Himalayas , is significantly different from 375 mg bd ( 750 mg ) of acetazolamide in the prevention of AMS , we design ed a prospect i ve , double-blind , r and omized , placebo-controlled trial . The participants were sample d from a diverse population of ( non-Nepali ) trekkers at Namche Bazaar ( 3440 m ) in Nepal on the Everest trekking route as they ascended to study midpoints ( 4280 m/4358 m ) and the endpoint , Lobuje ( 4928 m ) , where data were collected . Participants were r and omly assigned to receive 375 mg bd of acetazolamide ( 82 participants ) , 125 mg bd of acetazolamide ( 74 participants ) , or a placebo ( 66 participants ) , beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd ( 24 % vs. 21 % , 95 % confidence interval , -12.6 % , 19.8 % ) , in contrast to significantly greater AMS ( 51 % ) observed in the placebo group ( 95 % confidence interval for differences : 8 % , 46 % ; 12 % , 49 % for low and high comparisons , respectively ) . Both doses of acetazolamide improved oxygenation equally ( 82.9 % for 250 mg daily and 82.8 % for 750 mg daily ) , while placebo endpoint oxygen saturation was significantly less at 80.7 % ( 95 % confidence interval for differences : 0.5 % , 3.9 % and 0.4 % , 3.7 % for low and high comparisons , respectively ) . There was also more paresthesia in the 375-mg bd group ( p < 0.02 ) . We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS ; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 High-altitude hypoxia impedes cognitive performance . It is not well known whether the prophylactic use of acetazolamide for altitude sickness can influence cognitive performance at high altitude . When ascending to high altitude locations , one may face medical risks , including cognitive impairment , which may significantly hinder climbing abilities or exploratory behavior . Effective prophylactic drugs have rarely been reported . Because acetazolamide is commonly used to treat acute mountain sickness ( AMS ) , we assessed the potential effects of acetazolamide on cognitive performance during high-altitude exposure . Twenty-one volunteers aged 22 - 26 years were r and omized to receive a 4-day treatment of acetazolamide ( 125 mg Bid , n=11 ) or placebo ( n=10 ) before and after air travel from Xianyang ( 402 m ) to Lhasa ( 3561 m ) . Neuropsychological performance was assessed using the digit symbol substitution test ( DSST ) , paced auditory serial addition test ( PASAT ) , operation span task , and free recall test at 6 , 30 , and 54 h after arrival at Lhasa . The Lake Louise Score ( LLS ) was used to diagnose AMS . At high altitude , acetazolamide impaired rather than improved neuropsychological measures of concentration , cognitive processing speed , reaction time , short-term memory , and working memory , which were assessed by DSST , PASAT , and operation span task at 6 and 30 h after arrival ( p<0.05 ) . However , the prophylactic use of acetazolamide was found to reduce the incidence of AMS compared to the placebo ( p<0.05 ) . In conclusion , acetazolamide impairs neuropsychological function , at least in part , shortly after the ascent to high altitude OBJECTIVE High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers . Moreover , calcium entering in the cells could explain the congestive phenomena of acute mountain sickness ( AMS ) . These findings led us to study the action of a calcium channel blocker , isradipine , in the prevention of non-complicated AMS . METHODS In a double blind r and omized study , 20 healthy volunteers received 5 mg of isradipine ( n = 6 ) or placebo ( n = 6 ) for 8 days . After 5 days of treatment in normoxia , the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score , haemodynamic parameters and renal function . RESULTS The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia . Heart rate was an average of 15 b/min lower in the isradipine group , probably because of a direct action of isradipine on the sinus node . Otherwise , the effects of hypoxia were similar in both groups and were in accordance with the literature . There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to st and ing position . Renal blood flow , measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia . Cerebral blood flow was elevated , due to the direct vasodilator effect of hypoxia . However this increase did not seem to be the main mechanism responsible for the congestive phenomena . On the other h and , the increase in capillary permeability ( demonstrated by the increased transcapillary escape rate of albumin , and albuminuria ) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema . Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema OBJECTIVE To evaluate the efficacy of aspirin for headache when exercising during acute high-altitude exposure . BACKGROUND Aspirin effectively prevents headache when mostly resting during acute high-altitude exposure . However , the majority of individuals exposed to high altitude perform mountaineering activities , which might trigger headache . DESIGN R and omized , double-blind , placebo-controlled trial . METHODS Thirty-one healthy volunteers ( 20 men , 11 women ; aged 22 to 59 years ) were transported to an altitude of about 3000 meters and climbed up to 3800 meters . They then descended to a mountain hut at 3480 meters and spent 2 nights there . Tablets ( placebo or 320 mg aspirin ) were administered three times at 4-hour intervals , beginning 2 hours before arrival at high altitude . Headache scoring and measurements of heart rate , blood pressure , and arterial oxygen saturation were performed . RESULTS Ninety-three percent ( 14 of 15 ) of the placebo group and 56 % ( 9 of 16 ) of the aspirin group developed headache when mountaineering activities were performed during acute exposure to high altitude ( P<.05 ) . Five hours after arrival at high altitude , mean resting oxygen saturation was 86.1 % + /- 2.1 % with aspirin and 85.7 % + /- 2.8 % with placebo ( P = .66 ) . However , subjects in the aspirin group developed headache at saturation values less than or equal to 86 % , while those in the placebo group developed headache at saturation values less than 90 % . CONCLUSIONS Although the prophylactic intake of about 1 gram of aspirin reduced the headache incidence when exercising during acute high-altitude exposure , the incidence of headache was higher than previously shown for resting conditions . Aspirin result ed in tolerance to lower arterial oxygen saturation without development of headache ; exercise had the opposite effect BACKGROUND This double-blind , r and omized controlled trial aim ed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure . METHODS There were 138 healthy young male lowl and residents recruited and r and omly assigned to receive inhaled budesonide ( 200 μg , twice a day [ bid ] ) , oral dexamethasone ( 4 mg , bid ) , or placebo ( 46 in each group ) . They traveled to 3900 m altitude from 400 m by car . Medication started 1 day before high-altitude exposure and continued until the third day of exposure . Primary outcome measure was the incidence of acute mountain sickness after exposure . RESULTS One hundred twenty-four subjects completed the study ( 42 , 39 , and 43 in the budesonide , dexamethasone , and placebo groups , respectively ) . Demographic characteristics were comparable among the 3 groups . After high-altitude exposure , significantly fewer participants in the budesonide ( 23.81 % ) and dexamethasone ( 30.77 % ) groups developed acute mountain sickness compared with participants receiving placebo ( 60.46 % ) ( P = .0006 and P = .0071 , respectively ) . Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation ( SpO2 ) than the placebo group at altitude . Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group . Four subjects in the dexamethasone group reported adverse reactions . CONCLUSIONS Both inhaled budesonide ( 200 μg , bid ) and oral dexamethasone ( 4 mg , bid ) were effective for the prevention of acute mountain sickness , especially its severe form , compared with placebo . Budesonide caused fewer adverse reactions than dexamethasone Ibuprofen has been shown to be more effective than placebo in the treatment of high altitude headache ( HAH ) , but nonsteroidal anti-inflammatory agents have been linked to increased incidence of gastrointestinal ( GI ) side effects and high-altitude pulmonary edema ( HAPE ) . We postulated that acetaminophen , which does not share ibuprofen 's theorized causal link to GI side effects or HAPE , could provide effective HAH therapy . We conducted a prospect i ve , r and omized , double-blind , clinical trial of ibuprofen vs. acetaminophen in the Solu Khumbu , Nepal : Mt. Everest Base Camp , Pheriche , Dingboche ( 4240 m to 5315 m ) . Seventy-four consecutive patients ( ages 13 to 61 years ) were r and omized , were assessed with the Lake Louise Acute Mountain Sickness ( AMS ) criteria , and received a physical examination ( which included vital signs , oxygen saturation as measured by pulse oximetry ( SpO(2 ) ) , and assessment of clinical Lake Louise AMS criteria ) . Patients then received either 400 mg of ibuprofen ( IBU ) or 1000 mg of acetaminophen ( ACET ) , and were asked to rate their cephalgia using a 10-cm visual analog scale ( VAS ) . Thirty-nine patients received IBU , and 35 received ACET . Baseline Lake Louise AMS scores were identical in the two groups ( mean = 5.9 ) . No differences in mean VAS scores between IBU and ACET groups were noted at time 0 ( presentation ) , 30 , 60 , or 120 min . No cases of HAPE or high altitude cerebral edema were noted during the study period . In this study population , acetaminophen was as effective as ibuprofen in relieving the pain of HAH Sixty-four climbers participated in a r and omized clinical trial of acetazolamide prophylaxis for acute mountain sickness ( AMS ) during rapid , active ascent of MT Rainier . Twenty-nine ( 93.6 % ) of 31 climbers receiving acetazolamide and 25 ( 75.8 % ) of 33 receiving placebo attained the summit . Time spent ascending from sea level to the summit ( 4,394 m ) averaged 33.5 hours ( range , 23 to 48 hours ) . On the summit AMS was less common in climbers receiving acetazolamide , and they experienced less headache , nausea , drowsiness , shortness of breath , and dizziness and a greater sense of satisfaction and psychological well-being . Minute ventilation on the summit was significantly greater in subjects taking acetazolamide ( 24.9 + /- 2.0 L/min compared with 16.9 + /- 3.8 L/min ) . Expired vital capacity was also greater on the summit in the acetazolamide group ( 6.9 + /- 0.4 L compared with 5.8 + /- 0.4 L ) . We conclude that acetazolamide is effective in the prophylaxis of AMS for climbers attempting rapid , active ascent . Increased ventilation at altitude , producing an increased alveolar oxygen tension , may be related to the observed amelioration of symptoms Hypoxia is the main responsible factor initiating the symptoms of acute mountain sickness ( AMS ) in susceptible individuals . Measures that improve oxygenation and /or hasten acclimatization like pre-treatment with acetazolamide will prevent the development of AMS . We hypothesized that pre-treatment with acetazolamide the day before arrival at high altitude would elicit improved oxygenation compared to placebo not until the second day of high-altitude exposure . Fifteen study participants were r and omly assigned in a double blind fashion to receive placebo or acetazolamide ( 2 × 125 mg ) before ( 10 hours and 1 hour ) exposure to high altitude ( Monte Rosa plateau , 3480 m ) . Beside AMS scoring , heart rate , minute ventilation , and blood gas analyses were performed during rest and submaximal exercise at low altitude and on day 1 , 2 and 3 at high altitude . From low altitude to day 1 at high altitude changes of pH ( 7.41 ± 0.01 vs. 7.48 ± 0.04 ) and HCO3 ( 24.0 ± 0.46 vs. 24.6 ± 2.6 mmol/L ) within the placebo group differed significantly from those within the acetazolamide group ( 7.41 ± 0.01 vs. 7.41 ± 0.02 ; 23.6 ± 0.38 vs. 20.7 ± 1.8 mmol/L ) ( P < 0.05 ) . AMS incidence tended to be lower with acetazolamide ( P < 0.1 ) . From low altitude to day 2 at high altitude changes of paO2 within the placebo group ( 75.3 ± 5.4 vs. 40.5 ± 3.4 mmHg ) differed significantly from those within the acetazolamide group ( 76.5 ± 4.5 vs. 48.2 ± 4.9 mmHg ) ( P < 0.05 ) . In conclusion , pre-treatment with low-dose acetazolamide on the day before ascending to high altitude tended to reduce AMS incidence on the first day at high altitude but improved oxygen availability to tissues not until the second day of exposure . Therefore , it is suggested that the beginning of pre-treatment with low-dose acetazolamide at least two days before arrival at high altitude , in contrast to usual recommendations , would be of greater beneficial effect on AMS development BACKGROUND Exaggerated pulmonary-artery pressure due to hypoxic vasoconstriction is considered an important pathogenetic factor in high-altitude pulmonary edema . We previously found that nifedipine lowered pulmonary-artery pressure and improved exercise performance , gas exchange , and the radiographic manifestations of disease in patients with high-altitude pulmonary edema . We therefore hypothesized that the prophylactic administration of nifedipine would prevent its recurrence . METHODS Twenty-one mountaineers ( 1 woman and 20 men ) with a history of radiographically documented high-altitude pulmonary edema were r and omly assigned to receive either 20 mg of a slow-release preparation of nifedipine ( n = 10 ) or placebo ( n = 11 ) every 8 hours while ascending rapidly ( within 22 hours ) from a low altitude to 4559 m and during the following three days at this altitude . Both the subjects and the investigators were blinded to the assigned treatment . The diagnosis of pulmonary edema was based on chest radiography . Pulmonary-artery pressure was measured by Doppler echocardiography and the difference between alveolar and arterial oxygen pressure was measured in simultaneously sample d arterial blood and end-expiratory air . RESULTS Seven of the 11 subjects who received placebo but only 1 of the 10 subjects who received nifedipine had pulmonary edema at 4559 m ( P = 0.01 ) . As compared with the subjects who received placebo , those who received nifedipine had a significantly lower mean ( + /- SD ) systolic pulmonary-artery pressure ( 41 + /- 8 vs. 53 + /- 16 mm Hg , P = 0.01 ) , alveolar-arterial pressure gradient ( 6.6 + /- 3.8 vs. 11.8 + /- 4.4 mm Hg , P less than 0.001 ) , and symptom score of acute mountain sickness ( 2.0 + /- 0.7 vs. 3.9 + /- 1.9 , P less than 0.01 ) at 4559 m. CONCLUSIONS The prophylactic administration of nifedipine is effective in lowering pulmonary-artery pressure and preventing high-altitude pulmonary edema in susceptible subjects . These findings support the concept that high pulmonary-artery pressure has an important role in the development of high-altitude pulmonary edema The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness ( AMS ) and on overnight oxygenation , in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma , 6 males and 10 females , mean age 32 yrs , were first investigated at low altitude ( 760 m ) . They presented with mild airways obstruction , normal arterial blood gases , and normal oxygenation at night studied by pulse oximetry . After initial investigations , patients were divided by r and om number into the treated ( T ) and control ( C ) groups of eight patients each . T group patients received acetazolamide , 750 mg daily for 2 days , before the ascent and on the first day at altitude ( 3,200 m ) . Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry , performed on the first night at altitude , revealed that group T patients had statistically higher ( p < 0.05 ) initial , 91 vs 87 % , mean , 90 vs 86 % , and minimum , 84 vs 75 % , arterial oxygen saturation than group C patients . Overnight pulse oximetry was repeated on the 5th , 10th and 17th day at altitude , and showed that in group C patients , from the 5th day onwards , oxygenation improved to the level observed in group T patients on the first night . We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS , and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia STUDY OBJECTIVE Acute mountain sickness occurs in more than 25 % of the tens of millions of people who travel to high altitude each year . Previous studies on chemoprophylaxis with nonsteroidal anti-inflammatory drugs are limited in their ability to determine efficacy . We compare ibuprofen versus placebo in the prevention of acute mountain sickness incidence and severity on ascent from low to high altitude . METHODS Healthy adult volunteers living at low altitude were r and omized to ibuprofen 600 mg or placebo 3 times daily , starting 6 hours before ascent from 1,240 m ( 4,100 ft ) to 3,810 m ( 12,570 ft ) during July and August 2010 in the White Mountains of California . The main outcome measures were acute mountain sickness incidence and severity , measured by the Lake Louise Question naire acute mountain sickness score with a diagnosis of ≥ 3 with headache and 1 other symptom . RESULTS Eighty-six participants completed the study ; 44 ( 51 % ) received ibuprofen and 42 ( 49 % ) placebo . There were no differences in demographic characteristics between the 2 groups . Fewer participants in the ibuprofen group ( 43 % ) developed acute mountain sickness compared with those receiving placebo ( 69 % ) ( odds ratio 0.3 , 95 % confidence interval 0.1 to 0.8 ; number needed to treat 3.9 , 95 % confidence interval 2 to 33 ) . The acute mountain sickness severity was higher in the placebo group ( 4.4 [ SD 2.6 ] ) than individuals receiving ibuprofen ( 3.2 [ SD 2.4 ] ) ( mean difference 0.9 % ; 95 % confidence interval 0.3 % to 3.0 % ) . CONCLUSION Compared with placebo , ibuprofen was effective in reducing the incidence of acute mountain sickness Twenty-four amateur climbers took part in a double-blind controlled cross-over trial of acetazolamide versus placebo for the prevention of acute mountain sickness . They climbed Kilimanjaro ( 5895 m ) and Mt Kenya ( 5186 m ) in three weeks with five rest days between ascents . The severity of acute mountain sickness was gauged by a score derived from symptoms recorded daily by each subject . On kilimanjaro those taking acetazolamide reached a higher altitude ( 11 v 4 reached the summit ) and had a lower symptom score than those taking placebo ( mean 4.8 v 14.3 ) . Those who had taken acetazolamide on Kilimanjaro maintained their low symptom scores while taking placebo on Mt Kenya ( mean score 1.9 ) , whereas those who had taken placebo on Kilimanjaro experienced a pronounced improvement when they took acetazolamide on Mt Kenya ( mean score 2.5 ) . Acute mountain sickness prevented one subject for completing either ascent . Acetazolamide was acceptable to 23 of the 24 subjects . Acetazolamide is recommended as an acceptable and effective prophylactic for acute mountain sickness Methazolamide ( 150 mg/d ) was as effective as acetazolamide ( 500 mg/d ) in preventing the symptoms of acute mountain sickness in 20 subjects ascending to 4985 m. PaO2 and oxygen saturation levels were similar on the two drugs but the fall in PaCO2 was greater on acetazolamide . Paraesthesiae , a side-effect of carbonic anhydrase inhibitors , tended to be less at high altitude on methazolamide and was significantly less when taking 100 mg/d at low altitude . It is likely that paraesthesiae is similar on the two drugs when given in doses that affect blood gases equally Eighteen climbers actively ascended Mount Rainier ( elevation 4,392 m ) twice during a r and omized , double-blind , concurrent , placebo-controlled , crossover trial comparing the use of acetazolamide , 250 mg , dexamethasone , 4 mg , and placebo every 8 hours as prophylaxis for acute mountain sickness . Each subject was r and omly assigned to receive placebo during one ascent and one of the active medications during the other ascent . Assessment of acute mountain sickness was performed using the Environmental Symptoms Question naire and a clinical interview . At the summit or high point attained above base camp , the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms . Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone ( 0.26 + /- 0.16 and 0.20 + /- 0.19 , respectively ) were significantly lower than similar scores for both acetazolamide ( 0.80 + /- 0.80 and 1.20 + /- 1.05 ; P = 0.25 ) and placebo ( 1.11 + /- 1.02 and 1.45 + /- 1.27 ; P = .025 ) . Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects . Compared with placebo , dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent . The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known , but it can be considered for persons without contraindications who are intolerant of acetazolamide , for whom acetazolamide is ineffective , or who must make forced , rapid ascent to high altitude for a short period of time with a guaranteed retreat route Vuyk , Jaap , Jan Van Den Bos , Kees Terhell , Rene De Bos , Ad Vletter , Pierre Valk , Martie Van Beuzekom , Jack Van Kleef , and Albert Dahan . Acetazolamide improves cerebral oxygenation during exercise at high altitude . High Alt . Med . Biol . 7:290 - 301 , 2006.--Acute mountain sickness is thought to be triggered by cerebral hypoxemia and be prevented by acetazolamide ( Actz ) . The effect of Actz on cerebral oxygenation at altitude remains unknown . In 16 members of the 2005 Dutch Cho Oyu ( 8201 m , Tibet ) expedition , the influence of Actz and exercise ( 750 mg PO daily ) on heart rate , peripheral and regional cerebral oxygen saturation ( Sa(O(2 ) ) and rS(O(2 ) ) ) , the Lake Louise score ( LLS ) , and psychomotor function were studied at 0 m 14 days prior to the expedition , after arrival at 3700 m on day 3 , after arrival at 5700 m on day 29 , and again at 5700 m before the end of the expedition on day 51 . After arrival at 3700 m , the LLS of the climbers taking Actz ( n = 8) was significantly lower compared to those who did not take Actz ( n = 8) : 0.75 + /- 1.0 versus 2.9 + /- 2.0 , p < 0.05 ( ANOVA ) . High LLSs were associated with low rS(O(2 ) ) values in rest and exercise ( p < 0.01 and p < 0.001 ) . With altitude , resting Sa(O(2 ) ) and resting rS(O(2 ) ) decreased significantly ( p < 0.001 ) , irrespective of Actz use . Exercise at 3700 m and 5700 m reduced Sa(O(2 ) ) and rS(O(2 ) ) even further compared to rest ( p < 0.001 ) , although at 3700 m the rS(O(2 ) ) was preserved better in those who took Actz ( 55.3 + /- 4.3 % versus 47.9 + /- 5.7 % , p < 0.05 ) . Irrespective of Actz use , with altitude , the percentage of omissions in the vigilance and tracking test increased while the climbers ' scores on vigor decreased ( p < 0.05 ) . In conclusion , at altitude , exercise-induced reduction in cerebral oxygenation is less in climbers on Actz compared to climbers not taking Actz . This effect is nullified after several weeks at altitude due to acclimatization in climbers not taking Actz Acute mountain sickness is a syndrome that occurs when unacclimatized persons ascend rapidly to high altitudes . It is postulated that cerebral edema causes its symptoms . Since dexamethasone is useful in treating some forms of cerebral edema , we investigated its role in the prevention of acute mountain sickness . Using a double-blind crossover design , we exposed eight young men to a simulated altitude of 4570 m ( 15,000 ft ) on two occasions . By r and om assignment , each subject received dexamethasone ( 4 mg every 6 hours ) or placebo for 48 hours before and throughout the 42-hour exposure . The presence of symptoms of acute mountain sickness was established by two methods : a question naire and an interview by a physician . Dexamethasone significantly reduced the symptoms of acute mountain sickness . During dexamethasone treatment , the cerebral-symptom score ( mean + /- S.E. ) decreased from 1.09 + /- 0.18 to 0.26 + /- 0.08 , and the respiratory-symptom score decreased from 0.64 + /- 0.09 to 0.31 + /- 0.06 ( both , P less than 0.05 ) . As judged by the interviewing physician , the symptom score decreased from 1.10 + /- 0.11 to 0.28 + /- 0.07 ( P = 0.01 ) . We conclude that dexamethasone may be effective in preventing the symptoms of acute mountain sickness BACKGROUND Altitude-induced pulmonary hypertension has been suggested to cause left ventricular ( LV ) diastolic dysfunction due to ventricular interaction . In this study , we evaluate the effects of exercise- and altitude-induced increase in pulmonary artery pressures on LV diastolic function in an interventional setting investigating high-altitude pulmonary edema ( HAPE ) prophylaxis . METHODS Among 39 subjects , 29 were HAPE susceptible ( HAPE-S ) and 10 served as control subjects . HAPE-S subjects were r and omly assigned to prophylactic tadalafil ( 10 mg ) , dexamethasone ( 8 mg ) , or placebo bid , starting 1 day before ascent . Doppler echocardiography at rest and during submaximal exercise was performed at low altitude ( 490 m ) and high altitude ( 4,559 m ) . The ratio of early transmitral inflow peak velocity ( E ) to atrial transmitral inflow peak velocity ( A ) , pulmonary venous flow parameters , and tissue velocity within the septal mitral annulus during early diastole ( E ' ) were used to assess LV diastolic properties . LV filling pressures were estimated by E/E ' . Systolic right ventricular to atrial pressure gradients ( RVPGs ) were measured in order to estimate pulmonary artery pressures . RESULTS At 490 m , E/A decreased similarly with exercise in HAPE-S and control subjects ( HAPE-S , 1.5 + /- 0.3 to 1.3 + /- 0.3 ; control , 1.7 + /- 0.4 to 1.3 + /- 0.3 ; p = 0.12 between groups ) [ mean + /- SD ] , whereas RVPG increased significantly more in HAPE-S subjects ( 20 + /- 5 to 43 + /- 9 mm Hg vs 18 + /- 3 to 28 + /- 3 mm Hg , p < 0.001 ) . Changes in RVPG levels during exercise did not correlate with changes in E/A ( p > 0.1 ) . From 490 to 4,559 m , no correlations between changes in RVPG and changes in E/A or atrial reversal ( both p > 0.1 ) were observed . Neither of the groups showed an increase in E/E ' from 490 to 4,559 m. CONCLUSION Increased pulmonary artery pressure associated with exercise and acute exposure to 4,559 m appears not to cause LV diastolic dysfunction in healthy subjects . Therefore , ventricular interaction seems not to be of hemodynamic relevance in this setting AIMS We assessed the haemodynamic changes induced by exposure to high altitude hypoxia and the effects on them of acetazolamide , a drug prescribed to prevent and treat mountain sickness . METHODS AND RESULTS In 42 subjects ( 21 males , age 36.8 ± 8.9 years ) r and omized to double blind acetazolamide 250 mg b.i.d . or placebo , pulse wave velocity and pulse wave parameters were assessed ( PulsePen ) at baseline ; after 2-day treatment at sea level ; within 6 h and on 3rd day of exposure to high altitude . Exposure to high altitude significantly increased diastolic ( P < 0.005 ) and mean blood pressure ( BP ) ( P < 0.05 , after prolonged exposure ) in placebo but not in the acetazolamide group . Therefore , subjects on acetazolamide showed significantly lower values of diastolic ( P < 0.005 ) and mean BP ( P < 0.05 ) at altitude . Furthermore , they also showed significantly lower values of systolic BP ( P < 0.05 ) . Pulse wave velocity did not change at high altitude , while the augmentation index , normalized for a theoretical heart rate of 75 b.p.m . , significantly increased ( P < 0.05 ) under placebo , but not under acetazolamide . In a multivariate model , unadjusted augmentation index at high altitude was not affected by BP changes , while significant determinants were heart rate and gender . CONCLUSION Acute exposure to high altitude induced a rise in brachial BP and changes in pulse waveform-derived parameters , independent from changes in mean BP and partly counteracted by treatment with acetazolamide . The impact of acetazolamide on the haemodynamic alterations induced by hypobaric hypoxia may be considered among the beneficial effects of this drug in subjects prone to mountain sickness . CLINICAL TRIAL REGISTRATION EudraCT Number : 2010 - 019986 - 27 INTRODUCTION A higher risk of thrombosis has been reported on prolonged stay at high altitude ( HAA ) . Lowering of homocysteine ( Hcy ) has been found to reduce the risk of venous thrombosis . A r and omized field trial was conducted with primary question whether Hcy lowering agents have any effect on the incidence of thrombosis at HAA amongst Indian soldiers as compared to existing interventions . METHODS All units freshly inducted to HAA were r and omized into intervention ( Vit B12 1000 microgram/day , B6 3mg/day & folic acid 5mg/day ) and control arms , with a sample size of 12,000 person-years in each arm . RESULTS At the end of one year stay at HAA , Folate and B 12 levels decreased significantly in control arm . The levels of Hcy , fibrinogen and plasminogen activator inhibitor ( PAI 1 ) were lower and nitric oxide higher in intervention arm as compared to control arm ( p<0.05 ) . At the end of 2years , 5 thrombotic episodes occurred in the intervention arm and 17 in control arm with RR of 0.29 ( 95 % CI 0.11 - 0.80 ) , attributable fraction % ( AFe ) 70.59 % , Population attributable risk percent 54.55 % and Protective Fraction 240 % . CONCLUSION Intervention with B12 and folic acid is effective in reducing Hcy , PAI 1 , fibrinogen levels and increasing NO levels at 1yr as compared to control arm and reducing the incidence of thrombosis at 2years of stay at HAA . Thus , vitamin B 12 , B6 and folic acid intervention is safe and effective method of reducing morbidity and mortality caused by HAA induced coagulopathy OBJECTIVE High altitude headache ( HAH ) is the most common neurological complaint at altitude and the defining component of acute mountain sickness ( AMS ) . However , there is a paucity of literature concerning its prevention . Toward this end , we initiated a prospect i ve , double-blind , r and omized , placebo-controlled trial in the Nepal Himalaya design ed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH . METHODS Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg , acetazolamide 85 mg , or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity , AMS incidence and severity on the Lake Louise AMS Question naire ( LLQ ) , and visual analog scale ( VAS ) . RESULTS Two hundred sixty-five of 343 subjects completed the trial . HAH incidence was similar when treated with acetazolamide ( 27.1 % ) or ibuprofen ( 27.5 % ; P = .95 ) , and both agents were significantly more effective than placebo ( 45.3 % ; P = .01 ) . AMS incidence was similar when treated with acetazolamide ( 18.8 % ) or ibuprofen ( 13.7 % ; P = .34 ) , and both agents were significantly more effective than placebo ( 28.6 % ; P = .03 ) . In fully compliant participants , moderate or severe headache incidence was similar when treated with acetazolamide ( 3.8 % ) or ibuprofen ( 4.7 % ; P = .79 ) , and both agents were significantly more effective than placebo ( 13.5 % ; P = .03 ) . CONCLUSIONS Ibuprofen and acetazolamide were similarly effective in preventing HAH . Ibuprofen was similar to acetazolamide in preventing symptoms of AMS , an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness OBJECTIVES Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness ( AMS ) , but to date there have been no large r and omized trials investigating the efficacy of spironolactone in prevention of AMS . Hence , a prospect i ve , double-blind , r and omized , placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS . METHODS Participants were sample d from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach ( Nepal side ) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled , and 251 completed the trial from October to November 2007 . Participants were r and omly assigned to receive at least 3 doses of spironolactone 50 mg BID , acetazolamide 250 mg BID , or visually matched placebo . A Lake Louise AMS Score of 3 or more , together with the presence of headache and 1 other symptom , was used to evaluate the incidence and severity of AMS . Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache ( HAH ) . RESULTS Acetazolamide was more effective than spironolactone in preventing AMS ( OR = 0.28 , 95 % CI 0.12 - 0.60 , p < 0.01 ) . Spironolactone was not significantly different from placebo in the prevention of AMS . AMS incidence for placebo was 20.3 % , acetazolamide 10.5 % , and spironolactone 29.4 % . Oxygen saturation was also significantly increased in the acetazolamide group ( 83 % ± 0.04 ) vs spironolactone group ( 80 % ± 0.05 , p < 0.01 ) . CONCLUSIONS Spironolactone ( 50 mg BID ) was ineffective in comparison to acetazolamide ( 250 mg BID ) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya OBJECTIVE The effect of altitude on brain function is not yet well understood , nor is the influence of height and speed of ascent . Additionally , the relationship between acute mountain sickness ( AMS ) symptoms and brain function at altitude is unclear . We hypothesized that a deterioration from baseline measures of brain function occurs after rapid , mechanical ascent to 3459 m and would be less pronounced in persons taking acetazolamide . METHODS In this double blind , r and omized , placebo-controlled study , 20 healthy volunteers ( 14 men , 6 women ; mean age [ ±SD ] 43 ± 16 years ) were alternately allocated to acetazolamide 250 mg or to placebo , taken every 12 hours commencing 3 days before ascent . Prosaccadic and antisaccadic eye movements , heart rate , arterial saturation , and Lake Louise AMS scores were assessed at sea level and 15 to 22 hours after ascent to 3459 m. RESULTS Arterial oxygen saturation was significantly lower in the placebo group compared to the acetazolamide group at altitude ( Wilcoxon signed-rank test , median [ interquartile range ] : acetazolamide vs placebo : 92 % [ 5 ] vs 85 % [ 5 ] ; P = .007 ) , with no differences in prosaccadic latency , heart rate , or Lake Louise score . No differences in saccadic latencies from baseline to altitude were observed in the placebo group , whereas prosaccadic latencies were significantly longer at altitude with acetazolamide ( altitude vs baseline : 153 ms [ 41 ] vs 176 ms [ 52 ] , P = .008 ) . CONCLUSIONS Brain function , measured by saccadic eye movements , appears to be unimpaired after rapid ascent to 3459 m. Although acetazolamide improves oxygen saturations , it may worsen prosaccades , possibly indicating adverse effects of acetazolamide on brain function at moderate altitude Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema ( HAPE ) . Due to its effectiveness as a pulmonary vasodilator , sildenafil has been proposed as a prophylactic agent against HAPE . By conducting a parallel-group double blind , r and omized , placebo-controlled trial , we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure ( PASP ) and symptoms of acute mountain sickness ( AMS ) during acclimatization to high altitude . Sixty-two healthy lowl and volunteers ( 36 male ; median age 21 years , range 18 to 31 ) on the Apex 2 research expedition were flown to La Paz , Bolivia ( 3650 m ) , and after 4 - 5 days acclimatization ascended over 90 min to 5200 m. The treatment group ( n=20 ) received 50 mg sildenafil citrate three times daily . PASP was recorded by echocardiography at sea level and within 6 h , 3 days , and 1 week at 5200 m. AMS was assessed daily using the Lake Louise Consensus symptom score . On intention-to-treat analysis , there was no significant difference in PASP at 5200 m between sildenafil and placebo groups . Median AMS score on Day 2 at 5200 m was significantly higher in the sildenafil group ( placebo 4.0 , sildenafil 6.5 ; p=0.004 ) but there was no difference in prevalence of AMS between groups . Sildenafil administration did not affect PASP in healthy lowl and subjects at 5200 m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil . Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE . TRIALS REGISTRATION NUMBER : NCT00627965 The reduced arterial oxygen tension at high altitude impairs the ability to work . Acetazolamide improves arterial oxygen saturation ( SaO2 ) by increasing ventilation but is associated with an increased work and cost of breathing . Depending on the setting s , sildenafil can also increases SaO2 possibly through a reduction in pulmonary hypertension and interstitial edema , which could improve ventilation – perfusion matching . The objective of this study is to determine the effects of acetazolamide and sildenafil on ventilatory control and breathing efficiency ( VE/VCO2 ) during submaximal steady-state hypoxic exercise in healthy individuals . Following 18 h of hypoxic exposure in an altitude tent at an oxygen concentration of 12.5 % ( simulated altitude of 4,300 m ) , 15 participants performed 10 min of hypoxic exercise on a stationary bicycle at 40 % of their sea level peak oxygen uptake ( VO2 ) while r and omly receiving sildenafil 40 mg ( SIL ) , acetazolamide 125 mg ( ACZ ) or a placebo ( PLA ) . There was no difference in VO2 during exercise between conditions while SaO2 was greater with acetazolamide compared to both placebo and sildenafil . Acetazolamide increased ventilation ( PLA 49.0 ± 3.2 , SIL 47.7 ± 3.1 , ACZ 52.1 ± 3.0 l/min ) and reduced end-tidal CO2 ( PETCO2 ) ( PLA 32.1 ± 0.8 , SIL 32.8 ± 0.9 , ACZ 29.2 ± 0.7 mmHg ) compared to placebo and sildenafil . Breathing was less efficient with acetazolamide ( increased VE/VCO2 ) in comparison to placebo and sildenafil ( PLA 41.5 ± 1.0 , SIL 40.4 ± 1.3 , ACZ 45.4 ± 1.0 ) while sildenafil did not change VE/VCO2 during hypoxic exercise . In conclusion , acetazolamide increased ventilation and reduced breathing efficiency while sildenafil did not affect breathing efficiency despite a trend toward a blunted ventilatory response , possibly due to a reduction in pulmonary hypertension and /or ventilatory drive , during submaximal hypoxic exercise in healthy individuals RATIONALE Whether pulmonary hypertension at high altitude limits exercise capacity remains uncertain . OBJECTIVES To gain further insight into the pathophysiology of hypoxia induced pulmonary hypertension and the result ing reduction in exercise capacity , we investigated if the reduction in hypoxic pulmonary vasoconstrictive response with corticosteroids or phosphodiesterase-5 inhibition improves exercise capacity . METHODS A cardiopulmonary exercise test and echocardiography to estimate systolic pulmonary artery pressure were performed in 23 subjects with previous history of high altitude pulmonary edema , known to be associated with enhanced hypoxic vasoconstriction . Subjects were r and omized to dexamethasone 8 mg twice a day , tadalafil 10 mg twice a day , or placebo ( double-blinded ) , starting the day before ascent . MEASUREMENTS AND MAIN RESULTS Measurements were performed at low and high ( i.e. , 4,559 m ) altitude . Altitude exposure decreased maximum oxygen uptake and oxygen saturation , increased pulmonary artery pressure , and altered oxygen uptake kinetics . Compared with placebo , dexamethasone improved maximum oxygen uptake ( % predicted 74 + /- 13 % ; tadalafil 63 + /- 13 % , placebo 61 + /- 11 % ; P < 0.05 ) , oxygen kinetics ( mean response time 41 + /- 13 s ; tadalafil 46 + /- 6 s , placebo 45 + /- 10 s ; P < 0.05 ) , and reduced the ventilatory equivalent for CO(2 ) ( 42 + /- 4 ; tadalafil 49 + /- 4 , placebo 50 + /- 5 ; P < 0.01 ) . Peak oxygen saturation did not differ significantly between the three groups ( dexamethasone 66 + /- 7 % , placebo 62 + /- 7 % , tadalafil 69 + /- 5 % ; P = 0.08 ) . During echocardiography at low-intensity exercise ( 40 % of peak power ) , dexamethasone compared with placebo result ed in lower pulmonary artery pressure ( 47 + /- 9 mm Hg ; tadalafil 57 + /- 11 mm Hg , placebo 68 + /- 23 mm Hg ; P = 0.05 ) and higher oxygen saturation ( 74 + /- 7 % ; tadalafil 67 + /- 3 % , placebo 61 + /- 20 ; P < 0.02 ) . CONCLUSIONS Corticosteroids , but not phosphodiesterase-5 inhibition , partially prevented the limitation of exercise capacity in subjects with intense hypoxic pulmonary vasoconstriction at high altitude |
485 | 30,087,302 | The prevalence of OA was lower in participants with a higher adherence to a Mediterranean diet .
Biomarkers of inflammation and cartilage degradation related to OA were also analyzed and significant differences were detected only for IL1-α , which decreased in the MD group .
In conclusion , the three studies included in this systematic review demonstrated some relation between osteoarthritis and a Mediterranean diet . | Osteoarthritis ( OA ) affects 240 million people globally .
Few studies have examined the links between osteoarthritis and the Mediterranean diet ( MD ) .
The aim of this paper was to systematic ally review and analyze the epidemiological evidence in humans on the MD and its association with OA . | Objectives To investigate the effects of a Mediterranean type diet on patients with osteoarthritis ( OA ) . Participants Ninety-nine volunteers with OA ( aged 31 - 90 years ) completed the study ( 83 % female ) . Setting Southeast of Engl and , UK . Design Participants were r and omly allocated to the dietary intervention ( DIET , n = 50 ) or control ( CON , n = 49 ) . The DIET group were asked to follow a Mediterranean type diet for 16 weeks whereas the CON group were asked to follow their normal diet . Measurements All participants completed an Arthritis Impact Measurement Scale ( AIMS 2 ) pre- , mid- and post- study period . A subset of participants attended a clinic at the start and end of the study for assessment of joint range of motion , ROM ( DIET = 33 , CON = 28 ) , and to provide blood sample s ( DIET = 29 , CON = 25 ) for biomarker analysis ( including serum cartilage oligomeric matrix protein ( sCOMP ) ( a marker of cartilage degradation ) and a panel of other relevant biomarkers including pro- and anti-inflammatory cytokines ) . Results There were no differences between groups in the response of any AIMS 2 components and most biomarkers ( p > 0.05 ) , except the pro-inflammatory cytokine IL-1α , which decreased in the DIET group ( ~47 % , p = 0.010 ) . sCOMP decreased in the DIET group by 1 U/L ( ~8 % , p = 0.014 ) . There was a significant improvement in knee flexion and hip rotation ROM in the DIET group ( p < 0.05 ) . Conclusions The average reduction in sCOMP in the DIET group ( 1 U/L ) represents a meaningful change , but the longer term effects require further study The unsaponifiable fraction of olive oil from unripe fruits of Olea europaea at different stages of maturation ( from 20 to 32 weeks after flowering ) was analyzed by gas chromatography-mass spectrometry in order to select the time associated to the unsaponifiable fraction with the maximal yield in bioactive constituents . According to quantitative gas chromatography-mass spectrometry analysis , the unsaponifiable fraction ( 2.46 % of the total oil ) from olive fruits at the 22nd week was found to contain the maximal yield in anti-inflammatory constituents . Its composition was lanosterol ( 2.60 mg/g oil ) , stigmasterol ( 2.15 ) , cycloartanol acetate ( 2.04 ) , stigmastan-3,5-diene ( 2.01 ) , obtusifoliol ( 1.93 ) , cholesta-4,6-dien-3-one ( 1.42 ) , α-amyrin ( 1.42 ) , α-tocopherol ( 1.32 ) , squalene ( 1.02 ) , β-amyrin ( 0.57 ) , and β-sitosterol ( 0.22 ) . At later times , there was a decrease in the quantitative unsaponifiable fraction yield and a qualitative shift in the bioactive constituents . The 22nd week unsaponifiable fraction was subsequently incorporated into a topical preparation to be utilized for a small pilot clinical study in five patients affected by osteoarthrosis . According to clinical observation , the application of the ointment ( three times daily for three weeks ) attenuated h and and knee joint inflammatory features in all patients and was not associated to any adverse reactions Hydroxytyrosol is mainly found in olive leaves after hydrolysis of oleuropein and has anti-oxidant , anti-bacterial , and anti-inflammatory properties . The aim of this study was to investigate the effect of hydroxytyrosol for alleviating the pain in patients with gonarthrosis . We conducted a double-blind clinical trial in which hydroxytyrosol or placebo was administered to adult patients with gonarthrosis for 4 weeks . The group administered hydroxytyrosol showed significant improvement in the Japanese Orthopedic Association score ( pain measurement index ) and the visual analog scale score compared to the placebo group O steoarthritis ( OA ) is the most common type of arthritis , and the knee is the most common site of symptomatic OA . Knee OA is responsible for a higher incidence of disability than any other long-term conditions . Topical therapies present a therapeutic option for OA pain management . Nonsteroidal antiinflammatory drugs ( NSAIDs ) , salicylates , and capsaicin are currently the main topical therapies available . There is a need for safe and effective drugs for patients who do not respond well to conventional medical therapy . Indeed , such patients are turning increasingly to complementary/alternative medicines . One of the traditional methods for management of knee pain in some rural area of Iran is application of topical olive oil , as reported by Avicenna in his 10th-century book Canon of Medicine . Although the composition of olive oil is complex , the major groups of compounds thought to contribute to its observed health benefits include oleic acid , phenolics , and squalene , all of which have been reported to inhibit oxidative stress . Research ers reported beneficial effects of olive oil on rheumatoid arthritis after oral consumption . In 2005 , (j)-oleocanthal , the dialdehydic form of (j)-deacetoxy-ligstroside aglycone present in freshly pressed extra virgin olive oil , was shown to have properties of an NSAID . Although topical virgin olive oil is traditionally used in Iran in treating knee pain as an herbal medication , our survey did not find any scientific evaluation of its efficacy . Accordingly , we conducted a pilot prospect i ve , comparative , r and omized , doubleblinded trial of topical virgin olive oil therapy versus piroxicam gel in the treatment of knee OA . The report was prepared as recommended by the CONSORT statement and its elaboration on herbal interventions IMPORTANCE Knee osteoarthritis ( OA ) , a common cause of chronic pain and disability , has biomechanical and inflammatory origins and is exacerbated by obesity . OBJECTIVE To determine whether a ≥10 % reduction in body weight induced by diet , with or without exercise , would improve mechanistic and clinical outcomes more than exercise alone . DESIGN , SETTING , AND PARTICIPANTS Single-blind , 18-month , r and omized clinical trial at Wake Forest University between July 2006 and April 2011 . The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program . Participants were 454 overweight and obese older community-dwelling adults ( age ≥55 years with body mass index of 27 - 41 ) with pain and radiographic knee OA . INTERVENTIONS Intensive diet-induced weight loss plus exercise , intensive diet-induced weight loss , or exercise . MAIN OUTCOMES AND MEASURES Mechanistic primary outcomes : knee joint compressive force and plasma IL-6 levels ; secondary clinical outcomes : self-reported pain ( range , 0 - 20 ) , function ( range , 0 - 68 ) , mobility , and health-related quality of life ( range , 0 - 100 ) . RESULTS Three hundred ninety-nine participants ( 88 % ) completed the study . Mean weight loss for diet + exercise participants was 10.6 kg ( 11.4 % ) ; for the diet group , 8.9 kg ( 9.5 % ) ; and for the exercise group , 1.8 kg ( 2.0 % ) . After 18 months , knee compressive forces were lower in diet participants ( mean , 2487 N ; 95 % CI , 2393 to 2581 ) compared with exercise participants ( 2687 N ; 95 % CI , 2590 to 2784 , pairwise difference [Δ](exercise vs diet ) = 200 N ; 95 % CI , 55 to 345 ; P = .007 ) . Concentrations of IL-6 were lower in diet + exercise ( 2.7 pg/mL ; 95 % CI , 2.5 to 3.0 ) and diet participants ( 2.7 pg/mL ; 95 % CI , 2.4 to 3.0 ) compared with exercise participants ( 3.1 pg/mL ; 95 % CI , 2.9 to 3.4 ; Δ(exercise vs diet + exercise ) = 0.39 pg/mL ; 95 % CI , -0.03 to 0.81 ; P = .007 ; Δ(exercise vs diet ) = 0.43 pg/mL ; 95 % CI , 0.01 to 0.85 , P = .006 ) . The diet + exercise group had less pain ( 3.6 ; 95 % CI , 3.2 to 4.1 ) and better function ( 14.1 ; 95 % CI , 12.6 to 15.6 ) than both the diet group ( 4.8 ; 95 % CI , 4.3 to 5.2 ) and exercise group ( 4.7 ; 95 % CI , 4.2 to 5.1 , Δ(exercise vs diet + exercise ) = 1.02 ; 95 % CI , 0.33 to 1.71 ; P(pain ) = .004 ; 18.4 ; 95 % CI , 16.9 to 19.9 ; Δ(exercise vs diet + exercise ) , 4.29 ; 95 % CI , 2.07 to 6.50 ; P(function ) < .001 ) . The diet + exercise group ( 44.7 ; 95 % CI , 43.4 to 46.0 ) also had better physical health-related quality of life scores than the exercise group ( 41.9 ; 95 % CI , 40.5 to 43.2 ; Δ(exercise vs diet + exercise ) = -2.81 ; 95 % CI , -4.76 to -0.86 ; P = .005 ) . CONCLUSIONS AND RELEVANCE Among overweight and obese adults with knee OA , after 18 months , participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group ; those in the diet group had greater reductions in knee compressive force than those in the exercise group . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00381290 |
486 | 30,819,224 | Conclusions Trials of proportionate staged interventions are being used predominantly within the mental health field . | Background In proportionate or adaptive interventions , the dose or intensity can be adjusted based on individual need at predefined decision stages during the delivery of the intervention .
The development of such interventions may require an evaluation of the effectiveness of the individual stages in addition to the whole intervention .
However , evaluating individual stages of an intervention has various challenges , particularly the statistical design and analysis .
This review aim ed to identify the use of trials of proportionate interventions and how they are being design ed and analysed in current practice . | Background Depression accounts for the greatest burden of disease among all mental health problems , and is expected to become the second-highest amongst all general health problems by 2020 . By the age of 75 , 1 in 7 older people meet formal diagnostic criteria for depression . Efforts to ameliorate the burden of illness and personal suffering associated with depression in older people have focussed on those with more severe depressive syndromes . Less attention has been paid to those with mild disorders/sub-threshold depressive syndromes but these patients also suffer impairments in their quality of life and level of functioning . Methods / Design The CASPER study has been design ed to assemble an epidemiological cohort of people over 75 years of age ( the CASPER cohort ) , from which we will identify those eligible to participate in a trial of collaborative care for sub-threshold depression ( the CASPER trial).We aim to undertake a pragmatic r and omised controlled multi-centre trial evaluating the effectiveness and cost-effectiveness of collaborative care ; a low intensity psychological intervention in addition to usual general practitioner care versus usual general practitioner care alone . General practitioners from practice s based in the North of Engl and will be asked to identify potentially eligible patients over the age of 75 years . Patients will be sent a letter inviting them to participate in the study .We aim to recruit approximately 540 participants for the CASPER trial . A diagnostic interview will be carried out to ascertain trial eligibility with the major depressive episode module of the Mini International Neuropsychiatric Interview ( M.I.N.I. ) , eligible participants r and omised to either the intervention or usual care . The primary outcome will be measured with the Patient Health Question naire-9 ( PHQ-9 ) and additional quality of life measures will be collected . Data will be collected at baseline , 4 and 12 months for both trial and cohort participants .Trial Registration IS RCT N : IS RCT BACKGROUND Thus far collaborative stepped care ( CSC ) studies have not incorporated self-help as a first step . AIMS To evaluate the effectiveness of CSC in the treatment of common mental disorders . METHOD An 8-month cluster r and omised controlled trial comparing CSC to care as usual ( CAU ) ( Dutch Trial Register identifier NTR1224 ) . The CSC consisted of a stepped care approach guided by a psychiatric nurse in primary care with the addition of antidepressants dependent on the severity of the disorder , followed by cognitive-behavioural therapy in mental healthcare . RESULTS Twenty general practitioners ( GPs ) and 8 psychiatric nurses were r and omised to provide CSC or CAU . The GPs recruited 163 patients of whom 85 % completed the post-test measurements . At 4-month mid-test CSC was superior to CAU : 74.7 % ( n = 68 ) v. 50.8 % ( n = 31 ) responders ( P = 0.003 ) . At 8-month post-test and 12-month follow-up no significant differences were found as the patients in the CAU group improved as well . CONCLUSIONS Treatment within a CSC model result ed in an earlier treatment response compared with CAU Background Psychological distress is common in cancer survivors . Although there is some evidence on effectiveness of psychosocial care in distressed cancer patients , referral rate is low . Lack of adequate screening instruments in oncology setting s and insufficient availability of traditional models of psychosocial care are the main barriers . A stepped care approach has the potential to improve the efficiency of psychosocial care . The aim of the study described herein is to evaluate efficacy of a stepped care strategy targeting psychological distress in cancer survivors . Methods / design The study is design ed as a r and omized clinical trial with 2 treatment arms : a stepped care intervention programme versus care as usual . Patients treated for head and neck cancer ( HNC ) or lung cancer ( LC ) are screened for distress using OncoQuest , a computerized touchscreen system . After stratification for tumour ( HNC vs. LC ) and stage ( stage I/II vs. III/IV ) , 176 distressed patients are r and omly assigned to the intervention or control group . Patients in the intervention group will follow a stepped care model with 4 evidence based steps : 1 . Watchful waiting , 2 . Guided self-help via Internet or a booklet , 3 . Problem Solving Treatment administered by a specialized nurse , and 4 . Specialized psychological intervention or antidepressant medication . In the control group , patients receive care as usual which most often is a single interview or referral to specialized intervention . Primary outcome is the Hospital Anxiety and Depression Scale ( HADS ) . Secondary outcome measures are a clinical level of depression or anxiety ( CIDI ) , quality of life ( EQ-5D , EORTC QLQ-C30 , QLQ-HN35 , QLQ-LC13 ) , patient satisfaction with care ( EORTC QLQ-PATSAT ) , and costs ( health care utilization and work loss ( TIC-P and PRODISQ modules ) ) . Outcomes are evaluated before and after intervention and at 3 , 6 , 9 and 12 months after intervention . Discussion Stepped care is a system of delivering and monitoring treatments , such that effective , yet least re source -intensive , treatment is delivered to patients first . The main aim of a stepped care approach is to simplify the patient pathway , provide access to more patients and to improve patient well-being and cost reduction by directing , where appropriate , patients to low cost (self-)management before high cost specialist services . Trial registration Background Depressive and anxiety disorders are common in general practice but not always treated adequately . Introducing stepped care might improve this . In this r and omized trial we examined the effectiveness of such a stepped care model . Methods The study population consisted of primary care attendees aged 18 - 65 years with minor or major DSM-IV depressive and /or anxiety disorders , recruited through screening . We r and omized 120 patients to either stepped care or care as usual . The stepped care program consisted of ( 1 ) watchful waiting , ( 2 ) guided self-help , ( 3 ) short face-to-face Problem Solving Treatment and ( 4 ) pharmacotherapy and /or specialized mental health care . Patients were assessed at baseline and after 8 , 16 and 24 weeks . Results Symptoms of depression and anxiety decreased significantly over time for both groups . However , there was no statistically significant difference between the two groups ( IDS : P = 0.35 and HADS : P = 0.64 ) . The largest , but not significant , effect ( d = -0.21 ) was found for anxiety on T3 . In both groups approximately 48 % of the patients were recovered from their DSM-IV diagnosis at the final 6 months assessment . Conclusions In summary we could not demonstrate that stepped care for depression and anxiety in general practice was more effective than care as usual . Possible reasons are discussed . Trial Registration Current Controlled Trails : IS RCT N17831610 Hedges ( 2018 ) encourages us to consider asking new scientific questions concerning the optimization of adaptive interventions in education . In this commentary , we have exp and ed on this ( albeit briefly ) by providing concrete examples of scientific questions and associated experimental design s to optimize adaptive interventions , and commenting on some of the ways such design s might challenge us to think differently . A great deal of method ological work remains to be done . For example , we have only begun to consider experimental design and analysis methods for developing " cluster-level adaptive interventions " ( NeCamp , Kilbourne , & Almirall , 2017 ) , or to extend methods for comparing the marginal mean trajectories between the adaptive interventions embedded in a SMART ( Lu et al. , 2016 ) to accommo date r and om effects . These method ological advances , among others , will propel educational research concerning the construction of more complex , yet meaningful , interventions that are necessary for improving student and teacher outcomes Background Faced with a life-threatening illness , such as cancer , many patients develop stress symptoms , i.e. avoidance behaviour , intrusive thoughts and worry . Stress management interventions have proven to be effective ; however , they are mostly performed in group setting s and it is commonly breast cancer patients who are studied . We hereby present the design of a r and omized controlled trial ( RCT ) evaluating the effectiveness and cost-effectiveness of an individual stress-management intervention with a stepped-care approach in several cancer diagnoses . Method Patients ( ≥ 18 years ) with a recent diagnosis of breast cancer , colorectal cancer , lymphoma , prostate cancer or testicle cancer and scheduled for adjuvant/curative oncology treatment , will consecutively be included in the study . In this prospect i ve longitudinal intervention study with a stepped-care approach , patients will be r and omized to control , treatment as usual , or an individual stress-management intervention in two steps . The first step is a low-intensity stress-management intervention , given to all patients r and omized to intervention . Patients who continue to report stress symptoms after the first step will thereafter be given more intensive treatment at the second step of the programme . In the intervention patients will also be motivated to be physically active . Avoidance and intrusion are the primary outcomes . According to the power analyses , 300 patients are planned to be included in the study and will be followed for two years . Other outcomes are physical activity level , sleep duration and quality recorded objective ly , and anxiety , depression , quality of life , fatigue , stress in daily living , and patient satisfaction assessed using valid and st and ardized psychometric tested question naires . Utilization of hospital services will be derived from the computerized patient administration systems used by the hospital . The cost-effectiveness of the intervention will be evaluated through a cost-utility analysis . Discussion This RCT will provide empirical evidence of whether an individually administered stress-management programme in two steps can decrease stress as well as maintain or enhance patients ’ physical activity level , quality of life and psychological well-being . Further , this RCT , with a stepped-care approach , will provide knowledge regarding the cost-effectiveness of an individually administered stress-management programme whose aim is to help and support individual patients at the right level of care . Trial registration Clinical Trials.gov Identifier : NCT 01588262 Background This study compared the best available treatment for bulimia nervosa , cognitive – behavioural therapy ( CBT ) augmented by fluoxetine if indicated , with a stepped-care treatment approach in order to enhance treatment effectiveness . Aims To establish the relative effectiveness of these two approaches . Method This was a r and omised trial conducted at four clinical centres ( Clinical trials.gov registration number : NCT00733525 ) . A total of 293 participants with bulimia nervosa were r and omised to one of two treatment conditions : manual-based CBT delivered in an individual therapy format involving 20 sessions over 18 weeks and participants who were predicted to be non-responders after 6 sessions of CBT had fluoxetine added to treatment ; or a stepped-care approach that began with supervised self-help , with the addition of fluoxetine in participants who were predicted to be non-responders after six sessions , followed by CBT for those who failed to achieve abstinence with self-help and medication management . Results Both in the intent-to-treat and completer sample s , there were no differences between the two treatment conditions in inducing recovery ( no binge eating or purging behaviours for 28 days ) or remission ( no longer meeting DSM – IV criteria ) . At the end of 1-year follow-up , the stepped-care condition was significantly superior to CBT . Conclusions Therapist-assisted self-help was an effective first-level treatment in the stepped-care sequence , and the full sequence was more effective than CBT suggesting that treatment is enhanced with a more individualised approach BACKGROUND Exposure and response prevention ( ERP ) for obsessive-compulsive disorder ( OCD ) is underutilized , in part because of costs and time requirements . This study extends pilot work investigating the use of a stepped care ERP administration , in which patients are first given a low-intensity , low-cost treatment and the more costly intervention is reserved for those who do not respond to the first intervention . METHODS Thirty adults with OCD were r and omized to receive stepped care ERP or st and ard ERP . Those receiving stepped care started with three sessions over 6 weeks of low-intensity counseling with ERP bibliotherapy ; patients failing to meet strict responder criteria after 6 weeks were given the more traditional treatment of therapist-administered ERP ( 17 sessions twice weekly ) . Those receiving st and ard ERP received the therapist-administered ERP with no lower-intensity lead-in . RESULTS The two treatments were equally efficacious , with 67 % of stepped care completers and 50 % of st and ard treatment completers meeting criteria for clinical ly significant change at posttreatment . Similarly , no differences in client satisfaction ratings were obtained between the two groups . Examination of treatment costs , however , revealed that stepped care result ed in significantly lower costs to patients and third-party payers than did st and ard ERP , with large effect sizes . CONCLUSIONS These results suggest that stepped care ERP can significantly reduce treatment costs , without evidence of diminished treatment efficacy or patient satisfaction . Additional research is needed to determine the long-term efficacy and costs of stepped care for OCD , and to examine the financial and therapeutic impact of implementing stepped care in community setting Background A life threatening illness such as breast cancer can lead to a secondary diagnosis of PTSD ( post traumatic stress disorder ) with intrusive thoughts and avoidance as major symptoms . In a former study by the research group , 80 % of the patients with breast cancer reported a high level of stress symptoms close to the diagnosis , such as intrusive thoughts and avoidance behavior . These symptoms remained high throughout the study . The present paper presents the design of a r and omized study evaluating the effectiveness and cost-effectiveness of a stress management intervention using a stepped-care design . Method Female patients over the age of 18 , with a recent diagnosis of breast cancer and scheduled for adjuvant treatment in the form of chemotherapy , radiation therapy and /or hormonal therapy are eligible and will consecutively be included in the study . The study is a prospect i ve longitudinal intervention study with a stepped-care approach , where patients will be r and omised to one of two interventions in the final stage of treatment . The first step is a low intensity stress-management intervention that is given to all patients . Patients who do not respond to this level are thereafter given more intensive treatment at later steps in the program and will be r and omized to more intensive stress-management intervention in a group setting or individually . The primary out-come is subjective distress ( intrusion and avoidance ) assessed by the Impact of Event Scale ( IES ) . According to the power-analyses , 300 patients are planned to be included in the study and will be followed for one year . Other outcomes are anxiety , depression , quality of life , fatigue , stress in daily living and utilization of hospital services . This will be assessed with well-known psychometric tested question naires . Also , the cost-effectiveness of the intervention given in group or individually will be evaluated . Discussion This r and omized clinical trial will provide additional empirical evidence regarding the effectiveness of a stress-management program given in group or individually during adjuvant therapy in terms of decreased stress , minimizing fatigue , and maintaining or enhancing patients ’ quality of life and psychological well-being . Trial registration Clinical Trials.gov Identifier : Background Depression constitutes a significant public health burden and is associated is with high level of individual suffering . Insufficient human and material re sources impede the provision of adequate care for persons with the condition in low- and middle-income countries . It is commonly recognized that , to bridge this treatment gap , it is essential to integrate the treatment of depression into primary health care system . Methods / Design STEPCARE is a two-arm parallel cluster r and omized controlled trial to compare a stepped-care intervention package for depression in primary health care with care as usual in Nigeria . R and omization was conducted at the level of the participating primary health care clinics , while interventions are delivered to consenting individual participants who screen positive on the 9-item patient health question naire ( PHQ-9 score ≥ 11 ) and fulfil the DSM-IV criteria for major depression . Intervention delivered by trained primary health care workers ( PHCW ) supported by general physicians and psychiatrists as needed is in 3 steps determined by response to treatment . Each step consists of psychological interventions ( including psychoeducation , activity scheduling , social network reactivation and problem solving treatment ) offered to all participants and , depending on severity and response , medication . Primary outcome , assessed at 12 months following recruitment into the trial , is recovery from depression as shown by a PHQ-9 score of less than 6 . Secondary outcomes include changes in disability , quality of life and service utilization assessed at 6 and 12 months . Discussion The stepped care model examines the effectiveness of an intervention package for depression in which the intensity of treatment is determined by the clinical need of the patients . This approach is design ed to make the most efficient use of available re sources .Trial registration IS RCT N46754188 ( ISRTCN registry at isrtcn.com ; registered 23 September 2013 We present new statistical analyses of data arising from a clinical trial design ed to compare two-stage dynamic treatment regimes ( DTRs ) for advanced prostate cancer . The trial protocol m and ated that patients be initially r and omized among four chemotherapies , and that those who responded poorly be re-r and omized to one of the remaining c and i date therapies . The primary aim was to compare the DTRs ’ overall success rates , with success defined by the occurrence of successful responses in each of two consecutive courses of the patient ’s therapy . Of the 150 study participants , 47 did not complete their therapy as per the algorithm . However , 35 of them did so for reasons that precluded further chemotherapy , that is , toxicity and /or progressive disease . Consequently , rather than comparing the overall success rates of the DTRs in the unrealistic event that these patients had remained on their assigned chemotherapies , we conducted an analysis that compared viable switch rules defined by the per- protocol rules but with the additional provision that patients who developed toxicity or progressive disease switch to a non-prespecified therapeutic or palliative strategy . This modification involved consideration of bivariate per-course outcomes encoding both efficacy and toxicity . We used numerical scores elicited from the trial ’s principal investigator to quantify the clinical desirability of each bivariate per-course outcome , and defined one endpoint as their average over all courses of treatment . Two other simpler sets of scores as well as log survival time were also used as endpoints . Estimation of each DTR-specific mean score was conducted using inverse probability weighted methods that assumed that missingness in the 12 remaining dropouts was informative but explainable in that it only depended on past recorded data . We conducted additional worst- and best-case analyses to evaluate sensitivity of our findings to extreme departures from the explainable dropout assumption CONTEXT No r and omized trials have examined treatments for prescription opioid dependence , despite its increasing prevalence . OBJECTIVE To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment , with different counseling intensities , for patients dependent on prescription opioids . DESIGN Multisite , r and omized clinical trial using a 2-phase adaptive treatment research design . Brief treatment ( phase 1 ) included 2-week buprenorphine-naloxone stabilization , 2-week taper , and 8-week postmedication follow-up . Patients with successful opioid use outcomes exited the study ; unsuccessful patients entered phase 2 : extended ( 12-week ) buprenorphine-naloxone treatment , 4-week taper , and 8-week postmedication follow-up . SETTING Ten US sites . Patients A total of 653 treatment-seeking out patients dependent on prescription opioids . INTERVENTIONS In both phases , patients were r and omized to st and ard medical management ( SMM ) or SMM plus opioid dependence counseling ; all received buprenorphine-naloxone . MAIN OUTCOME MEASURES Predefined " successful outcome " in each phase : composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports . RESULTS During phase 1 , only 6.6 % ( 43 of 653 ) of patients had successful outcomes , with no difference between SMM and SMM plus opioid dependence counseling . In contrast , 49.2 % ( 177 of 360 ) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment ( week 12 ) , with no difference between counseling conditions . Success rates 8 weeks after completing the buprenorphine-naloxone taper ( phase 2 , week 24 ) dropped to 8.6 % ( 31 of 360 ) , again with no counseling difference . In secondary analyses , successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper ( 49.2 % [ 177 of 360 ] vs 8.6 % [ 31 of 360 ] , P < .001 ) . Chronic pain did not affect opioid use outcomes ; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone . CONCLUSIONS Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment ; if tapered off buprenorphine-naloxone , even after 12 weeks of treatment , the likelihood of an unsuccessful outcome is high , even in patients receiving counseling in addition to SMM OBJECTIVE To determine whether evidence -based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects . RESEARCH DESIGN AND METHODS This was a r and omized controlled trial of 387 diabetic patients ( 96.5 % Hispanic ) with clinical ly significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months . Intervention ( INT group ) included problem-solving therapy and /or antidepressant medication based on a stepped-care algorithm ; first-line treatment choice ; telephone treatment response , adherence , and relapse prevention follow-up over 12 months ; plus systems navigation assistance . Enhanced usual care ( EUC group ) included st and ard clinic care plus patient receipt of depression educational pamphlets and a community re source list . RESULTS INT patients had significantly greater depression improvement ( ≥50 % reduction in Symptom Checklist-20 depression score from baseline ; 57 , 62 , and 62 % vs. the EUC group 's 36 , 42 , and 44 % at 6 , 12 , and 18 months , respectively ; odds ratio 2.46–2.57 ; P < 0.001 ) . Mixed-effects linear regression models showed a significant study group – by – time interaction over 18 months in diabetes symptoms ; anxiety ; Medical Outcomes Study Short-Form Health Survey ( SF-12 ) emotional , physical , and pain-related functioning ; Sheehan disability ; financial situation ; and number of social stressors ( P = 0.04 for disability and SF-12 physical functioning , P < 0.001 for all others ) but no study group – by – time interaction in A1C , diabetes complications , self-care management , or BMI . CONCLUSIONS Socioculturally adapted collaborative depression care improved depression , functional outcomes , and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics Background Subthreshold depression and anxiety are common in the growing population of visually impaired older adults and increase the risk of full-blown depressive or anxiety disorders . Adequate treatment may prevent the development of depression or anxiety in this high risk group . Method / design A stepped-care programme was developed based on other effective interventions and focus groups with professionals and patient representatives of three low vision rehabilitation organisations in the Netherl and s and Belgium . The final programme consists of four steps : 1 ) watchful waiting , 2 ) guided self-help , 3 ) problem solving treatment , 4 ) referral to general practitioner . The (cost-)effectiveness of this programme is evaluated in a r and omised controlled trial . Patients ( N = 230 ) are r and omly assigned to either a treatment group ( stepped-care ) or a control group ( usual care ) . The primary outcome is the incidence of depressive and anxiety disorders , measured with the Mini International Neuropsychiatric Interview ( MINI ) . Discussion Preventive interventions for depression and anxiety have received little attention in the field of low vision . A stepped-care programme that focuses on both depression and anxiety has never been investigated in visually impaired older adults before . If the intervention is shown to be effective , this study will result in an evidence based treatment programme to prevent depression or anxiety in patients from low vision rehabilitation organisations . The pragmatic design of the study greatly enhances the generalisability of the results . However , a possible limitation is the difficulty to investigate the contribution of each individual step . Trial registration Identifier : Trials carried out in primary care typically involve complex interventions that require considerable planning if they are to be implemented successfully . The role of the statistician in promoting both robust study design and appropriate statistical analysis is an important contribution to a multi-disciplinary primary care research group . Issues in the design of complex interventions have been addressed in the Medical Research Council ’s new guidance document and over the past 7 years by the Royal Statistical Society ’s Primary Health Care Study Group . With the aim of raising the profile of statistics and building research capability in this area , particularly with respect to method ological issues , the study group meetings have covered a wide range of topics that have been of interest to statisticians and non-statisticians alike . The aim of this article is to provide an overview of the statistical issues that have arisen over the years related to the design and evaluation of trials in primary care , to provide useful examples and references for further study and ultimately to promote good practice in the conduct of complex interventions carried out in primary care and other health care setting s. Throughout we have given particular emphasis to statistical issues related to the design of cluster r and omised trials OBJECTIVE The authors evaluated an adaptive smoking cessation treatment strategy in which nicotine patch treatment was initiated before a quit date , and then , depending on initial therapeutic response , either the nicotine patch was continued or alternative pharmacotherapies were provided . METHOD The study was a double-blind , parallel-arm adaptive treatment trial . A total of 606 cigarette smokers started open-label nicotine patch treatment 2 weeks before the quit date . Those whose ad lib smoking did not decrease by > 50 % after 1 week were r and omly assigned to one of three double-blind treatments : nicotine patch alone ( control condition ) ; " rescue " treatment with bupropion augmentation of the patch ; or rescue treatment with varenicline alone . Participants whose precessation smoking decreased > 50 % but who lapsed after the quit date were also r and omly assigned to the two rescue treatments or to nicotine patch alone . Logistic regression analyses compared each rescue treatment against the control condition in terms of abstinence at the end of treatment ( weeks 8 - 11 ) and at 6 months . RESULTS Smokers who did not respond adequately to precessation nicotine patch benefited from bupropion augmentation ; abstinence rates at end of treatment were 16 % with nicotine patch alone and 28 % with bupropion augmentation ( odds ratio=2.04 , 95 % CI=1.03 - 4.01 ) . Switching to varenicline produced less robust effects , but point abstinence at 6 months was 6.6 % with the patch alone and 16.5 % with a switch to varenicline ( odds ratio=2.80 , 95 % CI=1.11 - 7.06 ) . Postquit adaptive changes in treatment had no significant effects on any abstinence outcome . CONCLUSIONS It is possible to rescue a significant portion of smokers who would have failed to achieve abstinence if left on nicotine patch alone by identifying these smokers before their quit date and implementing adaptive changes in treatment Background There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders . Methods Traditional r and omized controlled trials and statistical methods are not design ed to discover if , when , and to whom an intervention should be applied ; thus , other method ological approaches are needed that allow for the practice of personalized , evidence -based medicine with patients with bipolar depression . Results Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules , one per stage of clinical intervention , that map patient information to a recommended treatment . Using data from the acute depression r and omized care ( RAD ) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study , we estimate an optimal dynamic treatment regime via Q-learning . Conclusions The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a m and atory mood stabilizer Background Approximately 20–30 % of patients with cancer experience a clinical ly relevant level of emotional distress in response to disease and treatment . This in itself is alarming but it is even more problematic because it is often difficult for physicians and nurses to identify cancer patients who experience clinical ly relevant levels of anxiety and depression symptoms . This can result in persistent distress and can cause human suffering as well as costs for individuals and to the community . Methods Applying a multi-disciplinary and design -oriented approach aim ed at attaining new evidence -based knowledge in basic and applied psychosocial oncology , this protocol will evaluate an intervention to be implemented in clinical practice to reduce cancer patient anxiety and depression . A prospect i ve r and omized design will be used . The overarching goal of the intervention is to promote psychosocial health among patients suffering from cancer by means of self-help programmes delivered via an Internet platform . Another goal is to reduce costs for individuals and society , caused by emotional distress in response to cancer . Following screening to detect levels of patient distress , patients will be r and omized to st and ard care or a stepped care intervention . For patients r and omized to the intervention , step 1 will consist of self-help material , a chat forum where participants will be able to communicate with each other , and a Frequently Asked Questions ( FAQ ) section where they can ask questions and get answers from an expert . Patients in the intervention group who still report symptoms of anxiety or depression after access to step 1 will be offered step 2 , which will consist of cognitive behavioral therapy ( CBT ) administered by a personal therapist . The primary end point of the study is patients ’ levels of anxiety and depression , evaluated longitudinally during and after the intervention . Discussion There is a lack of controlled studies of the psychological and behavioral processes involved in this type of intervention for anxiety and depressive disorders . Since anxiety and depressive symptoms are relatively common in patients with cancer and the availability of adequate support efforts is limited , there is a need to develop evidence -based stepped care for patients with cancer , to be delivered via the Internet . Trial registration Clinical Trials.gov Identifier : CONTEXT Given the obesity epidemic , effective but re source -efficient weight loss treatments are needed . Stepped-treatment approaches customize interventions based on milestone completion and can be more effective while costing less to administer than conventional treatment approaches . OBJECTIVE To determine whether a stepped-care weight loss intervention ( STEP ) compared with a st and ard behavioral weight loss intervention ( SBWI ) would result in greater weight loss . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial of 363 overweight and obese adults ( body mass index : 25-<40 ; age : 18 - 55 years , 33 % nonwhite , and 83 % female ) who were r and omized to SBWI ( n = 165 ) or STEP ( n = 198 ) at 2 universities affiliated with academic medical centers in the United States ( Step-Up Study ) . Participants were enrolled between May 2008 and February 2010 and data collection was completed by September 2011 . INTERVENTIONS All participants were placed on a low-calorie diet , prescribed increases in physical activity , and attended group counseling sessions ranging from weekly to monthly during an 18-month period . The SBWI group was assigned to a fixed program . Counseling frequency , type , and weight loss strategies could be modified every 3 months for the STEP group in response to observed weight loss as it related to weight loss goals . MAIN OUTCOME MEASURE Mean change in weight over 18 months . Additional outcomes included resting heart rate and blood pressure , waist circumference , body composition , fitness , physical activity , dietary intake , and cost of the program . RESULTS Of the 363 participants r and omized , 260 ( 71.6 % ) provided a measure of mean change in weight over 18 months . The 18-month intervention result ed in weight decreasing from 93.1 kg ( 95 % CI , 91.0 to 95.2 kg ) to 85.6 kg ( 95 % CI , 83.4 to 87.7 kg ) ( P < .001 ) in the SBWI group and from 92.7 kg ( 95 % CI , 90.8 to 94.6 kg ) to 86.4 kg ( 95 % CI , 84.5 to 88.4 kg ) in the STEP group ( P < .001 ) . The percentage change in weight from baseline to 18 months was -8.1 % ( 95 % CI , -9.4 % to -6.9 % ) in the SBWI group ( P < .001 ) compared with -6.9 % ( 95 % CI , -8.0 % to -5.8 % ) in the STEP group ( P < .001 ) . Although the between-group difference in 18-month weight loss was not statistically different ( -1.3 kg [ 95 % CI , -2.8 to 0.2 kg ] ; P = .09 ) , there was a significant group × time interaction effect ( P = .03 ) . The cost per participant was $ 1357 ( 95 % CI , $ 1272 to $ 1442 ) for the SBWI group vs $ 785 ( 95 % CI , $ 739 to $ 830 ) for the STEP group ( P < .001 ) . Both groups had significant and comparable improvements in resting heart rate , blood pressure level , and fitness . CONCLUSIONS Among overweight and obese adults , the use of SBWI result ed in a greater mean weight loss than STEP over 18 months . Compared with SBWI , STEP result ed in clinical ly meaningful weight loss that cost less to implement . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00714168 Background Despite the availability of psychosocial evidence -based practice s ( EBPs ) , treatment and outcomes for persons with mental disorders remain suboptimal . Replicating Effective Programs ( REP ) , an effective implementation strategy , still result ed in less than half of sites using an EBP . The primary aim of this cluster r and omized trial is to determine , among sites not initially responding to REP , the effect of adaptive implementation strategies that begin with an External Facilitator ( EF ) or with an External Facilitator plus an Internal Facilitator ( IF ) on improved EBP use and patient outcomes in 12 months . Methods / Design This study employs a sequential multiple assignment r and omized trial ( SMART ) design to build an adaptive implementation strategy . The EBP to be implemented is life goals ( LG ) for patients with mood disorders across 80 community-based outpatient clinics ( N N = 1,600 patients ) from different U.S. regions . Sites not initially responding to REP ( defined as < 50 % patients receiving ≥3 EBP sessions ) will be r and omized to receive additional support from an EF or both EF/IF . Additionally , sites r and omized to EF and still not responsive will be r and omized to continue with EF alone or to receive EF/IF . The EF provides technical expertise in adapting LG in routine practice , whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice . The primary outcome is mental health-related quality of life ; secondary outcomes include receipt of LG sessions , mood symptoms , implementation costs , and organizational change . Discussion This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP . It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF.Trial registration Clinical Trials.gov identifier : OBJECTIVE This article presents an experimental design , the micror and omized trial , developed to support optimization of just-in-time adaptive interventions ( JITAIs ) . JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals ' health behaviors . Micror and omized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI . METHOD The article describes the micror and omized trial design , enumerates research questions that this experimental design can help answer , and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects . RESULTS Micror and omized trials enable causal modeling of proximal effects of the r and omized intervention components and assessment of time-varying moderation of those effects . CONCLUSION Micror and omized trials can help research ers underst and whether their interventions are having intended effects , when and for whom they are effective , and what factors moderate the interventions ' effects , enabling creation of more effective JITAIs Background The management of dizziness in older patients is primarily diagnosis-oriented . However , in 40 % of older patients with dizziness , GPs are not able to identify an underlying cause , and a number of common underlying causes of dizziness can not ( or hardly ) be treated . In this study we will investigate the effectiveness of a prognosis-oriented approach in the management of dizziness in older patients . This prognosis-oriented approach comprises identification of patients at risk for chronic dizziness with persistent impairment by identifying risk factors for an unfavourable course of dizziness . Patients at risk for chronic dizziness with persistent impairment will be offered treatment addressing the identified modifiable risk factors . Methods / Design This study will be performed in primary care . An intervention study and a validation study will be conducted in a three-arm cluster r and omised design . In the intervention study we will investigate a risk factor guided multi-component intervention . The risk factor guided intervention includes : ( 1 ) medication adjustment in case of three or more prescribed fall-risk-increasing drugs , ( 2 ) stepped care in case of anxiety disorder and /or depression , and ( 3 ) exercise therapy in case of impaired functional mobility . The primary outcome measure is dizziness-related impairment , which will be assessed with the Dizziness H and icap Inventory . Secondary outcome measures are quality of life , anxiety disorder and depression , use of fall-risk-increasing drugs , dizziness frequency , fall frequency , and healthcare utilization . Discussion This study is , to date , the first study that will investigate the effectiveness of a prognosis-oriented approach for reducing dizziness-related impairment in older people in primary care . Offering treatment that addresses identified modifiable risk factors to patients at high risk for chronic dizziness is unique . The pragmatic design of this study will enable evaluation of the outcomes in real-life routine practice conditions . An effective intervention will not only reduce dizziness-related impairment , but may also decrease healthcare utilization and healthcare costs . The previously developed risk score that will be vali date d alongside the intervention study will enable GPs to identify patients at high risk for chronic dizziness with persistent impairment . Trial registration Netherl and s Trial Register ( identifier : NTR4346 ) , registration date 15 December 2013 BACKGROUND There is clear evidence of the detrimental impact of hazardous alcohol consumption on the physical and mental health of the population . Estimates suggest that hazardous alcohol consumption annually accounts for 150,000 hospital admissions and between 15,000 and 22,000 deaths in the UK . In the older population , hazardous alcohol consumption is associated with a wide range of physical , psychological and social problems . There is evidence of an association between increased alcohol consumption and increased risk of coronary heart disease , hypertension and haemorrhagic and ischaemic stroke , increased rates of alcohol-related liver disease and increased risk of a range of cancers . Alcohol is identified as one of the three main risk factors for falls . Excessive alcohol consumption in older age can also contribute to the onset of dementia and other age-related cognitive deficits and is implicated in one-third of all suicides in the older population . OBJECTIVE To compare the clinical effectiveness and cost-effectiveness of a stepped care intervention against a minimal intervention in the treatment of older hazardous alcohol users in primary care . DESIGN A multicentre , pragmatic , two-armed r and omised controlled trial with an economic evaluation . SETTING General practice s in primary care in Engl and and Scotl and between April 2008 and October 2010 . PARTICIPANTS Adults aged ≥ 55 years scoring ≥ 8 on the Alcohol Use Disorders Identification Test ( 10-item ) ( AUDIT ) were eligible . In total , 529 patients were r and omised in the study . INTERVENTIONS The minimal intervention group received a 5-minute brief advice intervention with the practice or research nurse involving feedback of the screening results and discussion regarding the health consequences of continued hazardous alcohol consumption . Those in the stepped care arm initially received a 20-minute session of behavioural change counselling , with referral to step 2 ( motivational enhancement therapy ) and step 3 ( local specialist alcohol services ) if indicated . Sessions were recorded and rated to ensure treatment fidelity . MAIN OUTCOME MEASURES The primary outcome was average drinks per day ( ADD ) derived from extended AUDIT -- Consumption ( 3-item ) ( AUDIT-C ) at 12 months . Secondary outcomes were AUDIT-C score at 6 and 12 months ; alcohol-related problems assessed using the Drinking Problems Index ( DPI ) at 6 and 12 months ; health-related quality of life assessed using the Short Form Question naire-12 items ( SF-12 ) at 6 and 12 months ; ADD at 6 months ; quality -adjusted life-years ( QALYs ) ( for cost-utility analysis derived from European Quality of Life-5 Dimensions ) ; and health and social care re source use associated with the two groups . RESULTS Both groups reduced alcohol consumption between baseline and 12 months . The difference between groups in log-transformed ADD at 12 months was very small , at 0.025 [ 95 % confidence interval (CI)--0.060 to 0.119 ] , and not statistically significant . At month 6 the stepped care group had a lower ADD , but again the difference was not statistically significant . At months 6 and 12 , the stepped care group had a lower DPI score , but this difference was not statistically significant at the 5 % level . The stepped care group had a lower SF-12 mental component score and lower physical component score at month 6 and month 12 , but these differences were not statistically significant at the 5 % level . The overall average cost per patient , taking into account health and social care re source use , was £ 488 [ st and ard deviation ( SD ) £ 826 ] in the stepped care group and £ 482 ( SD £ 826 ) in the minimal intervention group at month 6 . The mean QALY gains were slightly greater in the stepped care group than in the minimal intervention group , with a mean difference of 0.0058 ( 95 % CI -0.0018 to 0.0133 ) , generating an incremental cost-effectiveness ratio ( ICER ) of £ 1100 per QALY gained . At month 12 , participants in the stepped care group incurred fewer costs , with a mean difference of -£194 ( 95 % CI -£585 to £ 198 ) , and had gained 0.0117 more QALYs ( 95 % CI -0.0084 to 0.0318 ) than the control group . Therefore , from an economic perspective the minimal intervention was dominated by stepped care but , as would be expected given the effectiveness results , the difference was small and not statistically significant . CONCLUSIONS Stepped care does not confer an advantage over minimal intervention in terms of reduction in alcohol consumption at 12 months post intervention when compared with a 5-minute brief ( minimal ) intervention . TRIAL REGISTRATION This trial is registered as IS RCT N52557360 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 25 . See the HTA programme website for further project information Objective : To examine the cost-effectiveness of the HIV Translating Initiatives for Depression Into Effective Solutions ( HITIDES ) intervention . Design : R and omized controlled effectiveness and implementation trial comparing depression collaborative care with enhanced usual care . Setting : Three Veterans Health Administration HIV clinics in the Southern United States . Subjects : Two hundred forty-nine HIV-infected patients completed the baseline interview ; 123 were r and omized to the intervention and 126 to usual care . Intervention : HITIDES consisted of an offsite HIV depression care team that delivered up to 12 months of collaborative care . The intervention used a stepped-care model for depression treatment , and specific recommendations were based on the Texas Medication Algorithm Project and the VA/Department of Defense Depression Treatment Guidelines . Main Outcome Measures : Quality -adjusted life years ( QALYs ) were calculated using the 12-Item Short Form Health Survey , the Quality of Well Being Scale , and by converting depression-free days to QALYs . The base case analysis used outpatient , pharmacy , patient , and intervention costs . Cost-effectiveness was calculated using incremental cost-effectiveness ratios ( ICERs ) and net health benefit . ICER distributions were generated using nonparametric bootstrap with replacement sampling . Results : The HITIDES intervention was more effective and cost saving compared with usual care in 78 % of bootstrapped sample s. The intervention net health benefit was positive and therefore deemed cost-effective using an ICER threshold of $ 50,000/QALY . Conclusions : In HIV clinic setting s , this intervention was more effective and cost saving compared with usual care . Implementation of offsite depression collaborative care programs in specialty care setting s may be a strategy that not only improves outcomes for patients but also maximizes the efficient use of limited health care re sources BACKGROUND Depression and anxiety disorders are common mental disorders worldwide . The MANAS trial aim ed to test the effectiveness of an intervention led by lay health counsellors in primary care setting s to improve outcomes of people with these disorders . METHODS In this cluster r and omised trial , primary care facilities in Goa , India , were assigned ( 1:1 ) by computer-generated r and omised sequence to intervention or control ( enhanced usual care ) groups . All adults who screened positive for common mental disorders were eligible . The collaborative stepped-care intervention offered case management and psychosocial interventions , provided by a trained lay health counsellor , supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist . The research assessor was masked . The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision ( ICD-10 ) at 6 months . This study is registered with Clinical Trials.gov , number NCT00446407 . FINDINGS 24 study clusters , with an equal proportion of public and private facilities , were r and omised equally between groups . 1160 of 1360 ( 85 % ) patients in the intervention group and 1269 of 1436 ( 88 % ) in the control group completed the outcome assessment . Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group ( n=620 [ 65·0 % ] vs 553 [ 52·9 % ] ; risk ratio 1·22 , 95 % CI 1·00 - 1·47 ; risk difference=12·1 % , 95 % CI 1·6%-22·5 % ) . The intervention had strong evidence of an effect in public facility attenders ( 369 [ 65·9 % ] vs 267 [ 42·5 % ] , risk ratio 1·55 , 95 % CI 1·02 - 2·35 ) but no evidence for an effect in private facility attenders ( 251 [ 64·1 % ] vs 286 [ 65·9 % ] , risk ratio 0·95 , 0·74 - 1·22 ) . There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group . None of the deaths were from suicide . INTERPRETATION A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities . FUNDING The Wellcome Trust Background Co-morbid major depression is a significant problem among patients with type 2 diabetes mellitus and /or coronary heart disease and this negatively impacts quality of life . Subthreshold depression is the most important risk factor for the development of major depression . Given the highly significant association between depression and adverse health outcomes and the limited capacity for depression treatment in primary care , there is an urgent need for interventions that successfully prevent the transition from subthreshold depression into a major depressive disorder . Nurse led stepped-care is a promising way to accomplish this . The aim of this study is to evaluate the cost-effectiveness of a nurse-led indicated stepped-care program to prevent major depression among patients with type 2 diabetes mellitus and /or coronary heart disease in primary care who also have subthreshold depressive symptoms . Methods / design An economic evaluation will be conducted alongside a cluster-r and omized controlled trial in approximately thirty general practice s in the Netherl and s. R and omization takes place at the level of participating practice nurses . We aim to include 236 participants who will either receive a nurse-led indicated stepped-care program for depressive symptoms or care as usual . The stepped-care program consists of four sequential but flexible treatment steps : 1 ) watchful waiting , 2 ) guided self-help treatment , 3 ) problem solving treatment and 4 ) referral to the general practitioner . The primary clinical outcome measure is the cumulative incidence of major depressive disorder as measured with the Mini International Neuropsychiatric Interview . Secondary outcomes include severity of depressive symptoms , quality of life , anxiety and physical outcomes . Costs will be measured from a societal perspective and include health care utilization , medication and lost productivity costs . Measurements will be performed at baseline and 3 , 6 , 9 and 12 months . Discussion The intervention being investigated is expected to prevent new cases of depression among people with type 2 diabetes mellitus and /or coronary heart disease and subthreshold depression , with subsequent beneficial effects on quality of life , clinical outcomes and health care costs . When proven cost-effective , the program provides a viable treatment option in the Dutch primary care system . Trial registration Dutch Trial Register Background Chronic Obstructive Pulmonary Disease ( COPD ) and asthma are common chronic diseases that are frequently accompanied by depression and /or anxiety . However , symptoms of depression and anxiety are often not recognized and therefore not treated . Currently , only a few studies have tested new clinical approaches that could improve the treatment of co-morbid depression and anxiety in these groups of patients . Methods / design The present r and omized controlled study will be conducted within the framework of PoZoB ( Praktijk Ondersteuning Zuid-Oost Brabant ) , a large primary care organization in the Netherl and s. Patients with asthma/ COPD and co-morbid anxiety/depression will be included in order to test the effectiveness of a disease management approach to treat these co-morbid disorders . Important elements of this approach are : 1 ) systematic screening to improve detection of anxiety and depression 2 ) treatment in case of positive screening 3 ) monitoring of anxiety and depression 4 ) intensified treatment in case of non-remission ( stepped care ) . Discussion The present study is a large primary care study on the treatment of co-morbid depression and anxiety in patients with asthma and COPD . Strengths of this study are its r and omized design , the focus on implementation in primary care and the fact that it applies the latest findings on the treatment of depression and anxiety . First results are expected in 2012/2013.Trial registration Netherl and s Trial Register ( NTR ) : Abstract Background Families of children living with chronic illness are more vulnerable to mental health problems , however this can be ameliorated by a family ’s resilience . The Child Illness and Resilience Program ( CHiRP ) will develop and evaluate a parent-focussed family intervention design ed to increase the resilience and wellbeing of families living with childhood chronic illness . Methods / Design The study will be conducted in an Australian regional paediatric hospital and will use a stepped care intervention that increases in intensity according to parental distress . All parents of children discharged from the hospital will receive a family resilience and wellbeing factsheet ( Step 1 ) . Parents of children attending selected outpatient clinics will receive a family resilience and wellbeing activity booklet ( Step 2 ) . Parents who receive the booklet and report psychological distress at three-month follow-up will be r and omised to participate in a family resilience information support group or waitlist control ( Step 3 ) . The Step 3 control group will provide data to compare the relative effectiveness of the booklet intervention alone versus the booklet combined with the group intervention for distressed parents . These participants will then receive the information support group intervention . All parents in Step 2 and 3 will complete baseline , post-intervention and six month follow up assessment s. The primary outcomes of the study will be changes in scores between baseline and follow-up assessment s on measures of constructs of family resilience , including parental wellbeing , family functioning , family beliefs and perceived social support . Qualitative feedback regarding the utility and acceptability of the different intervention components will also be collected . Discussion It is hypothesised that participation in the CHiRP intervention will be associated with positive changes in the key outcome measures . If effective , CHiRP will provide an opportunity for the health sector to deliver a st and ardised stepped care mental health promotion intervention to families living with childhood chronic illness . Trial registration Australian clinical Trials Registry ACTRN 12613000844741 Universal Trial Number ( UTN ) : 1111 - 1142 - Background Psychological distress ( i.e. depression and anxiety ) is a strong predictor of functional status and other aspects of quality of life in autologous stem cell transplantation following high-dose chemotherapy . Treatment of psychological distress is hypothesized to result in improvement of functional status and other aspects of quality of life . The aim is to evaluate the outcome of stepped care for psychological distress on functional status and other aspects of quality of life in patients with hematological malignancy treated with autologous stem cell transplantation . Methods / Design The study is design ed as a r and omized clinical trial with 2 treatment arms : a stepped care intervention program versus care as usual . Patients are r and omized immediately pre transplant . Stepped care and care as usual are initiated after a 6 weeks buffer period . Outcome is evaluated at 13 , 30 , and 42 weeks post transplant . In the experimental group , the first step includes an Internet-based self-help program . If psychological distress persists after the self-help intervention , the second step of the program is executed , i.e. a diagnostic evaluation and a st and ardized interview , yielding a problem analysis . Based on this information , a contract is made with the patient and treatment is provided consisting of individual face-to-face counseling , medication , or referral to other services . Care as usual comprises an interview with the patient , on ad hoc basis ; emotional support and advice , on ad hoc basis ; if urgent problems emerge , the patient is referred to other services . Primary outcome variables are psychological distress and functional status . Data are analyzed according to the intention to treat-principle . Discussion This study has several innovative characteristics . First , the outcome of the intervention for psychological distress in patients with hematological malignancy treated with autologous stem cell transplantation is evaluated in a r and omized controlled study . Second , the impact of the intervention on functional status is evaluated : it is hypothesized that reduction of psychological distress results in improved functional status . Furthermore , the intervention concerns an Internet-based treatment in the first step . Finally , the intervention is characterized by an emphasis on self-management , efficiency , and a multi-disciplinary approach with nurses taking up a central role . Trial Registration Background : Collaborative stepped care ( CSC ) may be an appropriate model to provide evidence -based treatment for anxiety disorders in primary care . Methods : In a cluster r and omised controlled trial , the effectiveness of CSC compared to care as usual ( CAU ) for adults with panic disorder ( PD ) or generalised anxiety disorder ( GAD ) in primary care was evaluated . Thirty-one psychiatric nurses who provided their services to 43 primary care practice s in the Netherl and s were r and omised to deliver CSC ( 16 psychiatric nurses , 23 practice s ) or CAU ( 15 psychiatric nurses , 20 practice s ) . CSC was provided by the psychiatric nurses ( care managers ) in collaboration with the general practitioner and a consultant psychiatrist . The intervention consisted of 3 steps , namely guided self-help , cognitive behavioural therapy and antidepressants . Anxiety symptoms were measured with the Beck Anxiety Inventory ( BAI ) at baseline and after 3 , 6 , 9 and 12 months . Results : We recruited 180 patients with a DSM-IV diagnosis of PD or GAD , of whom 114 received CSC and 66 received usual primary care . On the BAI , CSC was superior to CAU [ difference in gain scores from baseline to 3 months : -5.11 , 95 % confidence interval ( CI ) -8.28 to -1.94 ; 6 months : -4.65 , 95 % CI -7.93 to -1.38 ; 9 months : -5.67 , 95 % CI -8.97 to -2.36 ; 12 months : -6.84 , 95 % CI -10.13 to -3.55 ] . Conclusions : CSC , with guided self-help as a first step , was more effective than CAU for primary care patients with PD or GAD BACKGROUND The current nonr and omized clinical trial explored changes over time in children with an anxiety disorder during stepped care , manual-based cognitive behaviour therapy ( CBT ) . METHODS Clinical ly anxious children ( 8 - 12 years , n = 133 ) and their parents participated in child focused CBT ( 10 sessions ) . If assessment s indicated additional treatment was necessary , participants could step up to a second and possibly third treatment phase ( each 5 sessions ) including more parental involvement . RESULTS After the first treatment phase 45 % of the Intention-To-Treat sample was free of any anxiety disorder ; after the second and third phase an additional 17 % and 11 % respectively . In total , 74 % of the children no longer met criteria for any anxiety disorder following treatment . Child and parent reported anxiety and depression symptoms of children improved significantly during all treatment phases , as well as child reported anxiety sensitivity and negative affect . Children participating in more treatment showed significant improvements during additional treatment phases , indicating that late change occurred for the subgroup that had not changed during the first phase . CONCLUSIONS Stepped care offers a st and ardized , assessment based , yet tailored treatment approach for children with anxiety disorders . A more intensive treatment is offered when initial CBT is insufficient , providing children additional opportunities to reach the desired outcome Where patients receive therapy as a group , there are good theoretical reasons to believe that variation in the outcome will be smaller for patients treated in the same group than for patients treated in different groups . Similarly , where different therapists treat different groups of patients , outcome for patients treated by the same therapist may differ less than outcome for patients treated by different therapists . Clinical trials evaluating such therapies need to consider this potential lack of independence . As with cluster-r and omized trials , this has implication s for the precision of treatment effects estimates and statistical power . There are nevertheless differences between clustering due to the organization of treatment and that due to r and omization . In cluster-r and omized trials the distribution of cluster sizes in each treatment arm should be similar as a consequence of r and omization unless there is differential loss to follow-up . With clustering due to therapy group or therapist , cluster size may differ systematic ally between treatment arms , due to size of therapy groups or differing health professional caseload . Intra-cluster correlation may also differ between treatment arms . The implication s of differential cluster size and intracluster correlation for design and analysis will be illustrated by data from two trials , the first comparing nurse practitioner care with general practitioner care , and the second comparing a group therapy with individual treatment as usual . The special case where a group therapy or therapist is compared with an unclustered treatment is examined in detail using a simulation study . The implication s of differential clustering effects for sample size and power are addressed . It is argued that the design and analysis of this type of trial should take account of possible heterogeneity in cluster size and intracluster correlation BACKGROUND This study aim ed to determine the feasibility and the effectiveness of a Stepped Care Program ( SCP ) for preventing relapse of depression in older people . Stepped care consisted of ( 1 ) watchful waiting ; ( 2 ) bibliotherapy ; ( 3 ) individual cognitive behavioral therapy ; and ( 4 ) indicated treatment . METHODS In a r and omized controlled trial , persons 55 years and older ( n = 136 ) who had suffered at least one episode of major depression in the past received a SCP or Care As Usual ( CAU ) . The primary outcome measure was incidence of a new depressive episode . RESULTS Of 1725 previously depressed persons , 175 were willing to partake in the study , 136 of whom were eligible . Treatment satisfaction for stepped care was high . At 12-month follow-up , no difference in incidence of depression between SCP and CAU was found . Medical patient records showed that missing data were often related to relapse . CONCLUSIONS In this study , SCP was not more effective in preventing relapse than CAU . Watchful waiting may harmfully delay actual preventive treatment . Prevention as an integral part of regular treatment might lead to higher participation rates In recent years , research in the area of intervention development has been shifting from the traditional fixed-intervention approach to adaptive interventions , which allow greater individualization and adaptation of intervention options ( i.e. , intervention type and /or dosage ) over time . Adaptive interventions are operationalized via a sequence of decision rules that specify how intervention options should be adapted to an individual 's characteristics and changing needs , with the general aim to optimize the long-term effectiveness of the intervention . Here , we review adaptive interventions , discussing the potential contribution of this concept to research in the behavioral and social sciences . We then propose the sequential multiple assignment r and omized trial ( SMART ) , an experimental design useful for addressing research questions that inform the construction of high- quality adaptive interventions . To clarify the SMART approach and its advantages , we compare SMART with other experimental approaches . We also provide methods for analyzing data from SMART to address primary research questions that inform the construction of a high- quality adaptive intervention OBJECTIVE To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain . METHODS R and omized controlled effectiveness trial using stepped care methodology . Participants are ≥60 years old . Phase 1 ( 6 weeks ) is open treatment with venlafaxine xr 150 mg/day and supportive management ( SM ) . Response is 2 weeks of PHQ-9 ≤5 and at least 30 % improvement in the average numeric rating scale for pain . Nonresponders progress to phase 2 ( 14 weeks ) in which they are r and omized to high-dose venlafaxine xr ( up to 300 mg/day ) with problem solving therapy for depression and pain ( PST-DP ) or high-dose venlafaxine xr and continued SM . Primary outcomes are the univariate pain and depression response and both observed and self-reported disability . Survival analytic techniques will be used , and the clinical effect size will be estimated with the number needed to treat . We hypothesize that self-efficacy for pain management will mediate response for subjects r and omized to venlafaxine xr and PST-DP . RESULTS Not applicable . CONCLUSIONS The results of this trial will inform the care of these complex patients and further underst and ing of comorbid pain and depression in late life OBJECTIVE Over the past 2 decades , colleges and universities have seen a large increase in the number of students referred to the administration for alcohol policies violations . However , a substantial portion of m and ated students may not require extensive treatment . Stepped care may maximize treatment efficiency and greatly reduce the dem and s on campus alcohol programs . METHOD Participants in the study ( N = 598 ) were college students m and ated to attend an alcohol program following a campus-based alcohol citation . All participants received Step 1 : a 15-min brief advice session that included the provision of a booklet containing advice to reduce drinking . Participants were assessed 6 weeks after receiving the brief advice , and those who continued to exhibit risky alcohol use ( n = 405 ) were r and omized to Step 2 , a 60- to 90-min brief motivational intervention ( n = 211 ) , or an assessment -only control ( n = 194 ) . Follow-up assessment s were conducted 3 , 6 , and 9 months after Step 2 . RESULTS Results indicated that the participants who received a brief motivational intervention showed a significantly reduced number of alcohol-related problems compared to those who received assessment only , despite no significant group differences in alcohol use . In addition , low-risk drinkers ( n = 102 ; who reported low alcohol use and related harms at 6-week follow-up and were not r and omized to stepped care ) showed a stable alcohol use pattern throughout the follow-up period , indicating they required no additional intervention . CONCLUSION Stepped care is an efficient and cost-effective method to reduce harms associated with alcohol use by m and ated students OBJECTIVE Adolescents with Anorexia Nervosa ( AN ) , treated with family-based treatment ( FBT ) who fail to gain 2.3 kg by the fourth week of treatment have a 40 - 50 % lower chance of recovery than those who do . Because of the high risk of developing enduring AN , improving outcomes in this group of poor responders is essential . This study examines the feasibility and effects of a novel adaptive treatment ( i.e. , Intensive Parental Coaching-IPC ) aim ed at enhancing parental self-efficacy related to re-feeding skills in poor early responders to FBT . METHOD 45 adolescents ( 12 - 18 years of age ) meeting DSM TR IV criteria for AN were r and omized in an unbalanced design ( 10 to st and ard FBT ; 35 to the adaptive arm ) . Attrition , suitability , expectancy rates , weight change , and psychopathology were compared between groups . OUTCOMES There were no differences in rates of attrition , suitability , expectancy ratings , or most clinical outcomes between r and omized groups . However , the group of poor early responders that received IPC achieved full weight restoration ( > 95 % of expected mean BMI ) by EOT at similar rates as those who had responded early . CONCLUSIONS The results of this study suggest that it is feasible to use an adaptive design to study the treatment effect of IPC for those who do not gain adequate weight by session 4 of FBT . The results also suggest that using IPC for poor early responders significantly improves weight recovery rates to levels comparable to those who respond early . A sufficiently powered study is needed to confirm these promising findings AIMS Recent guidelines for the management of hypertension recommend an individualised stepped-care treatment approach in mild-to-moderate hypertensive patients , to achieve blood pressure ( BP ) goals . This study evaluated the probability of patients achieving BP targets with an aliskiren-based stepped-care treatment regimen . METHODS This was a 24-week , open-label , non-comparator study design that included six sequential 4-week treatment periods in patients with mild-to-moderate hypertension . Over the potential 24 weeks of active treatment , incremental therapy included the following add-on therapies at 4-week intervals : aliskiren 150 - 300 mg once daily , hydrochlorothiazide ( HCTZ ) 12.5 - 25 mg once daily , and finally amlodipine 5 - 10 mg once daily , as needed to achieve target BP . Subjects achieving BP targets following any given 4 weeks of therapy were considered study completers , while subjects not achieving their clinical BP target entered into the next step of incremental therapy . The primary efficacy end-point was the estimated cumulative probability of patients achieving BP target . RESULTS Of 256 patients treated , 232 ( 90.6 % ) completed the study . Baseline mean sitting BP was 155.7/91.7 mmHg . At study end-point , the estimated cumulative probability of reaching BP target was 86.12 % . The stepped-care treatment regimen was well tolerated at the maximal recommended doses of all the individual complimentary therapies . CONCLUSION An aliskiren-based stepped-care treatment regimen that subsequently included both HCTZ and amlodipine is effective in achieving BP goals in approximately 90 % of patients with mild-to-moderate hypertension A dynamic treatment regime ( DTR ) is a sequence of decision rules , each of which recommends a treatment based on a patient 's past and current health status . Sequential , multiple assignment , r and omized trials ( SMARTs ) are multi-stage trial design s that yield data specifically for building effective DTRs . Modeling the marginal mean trajectories of a repeated- measures outcome arising from a SMART presents challenges , because traditional longitudinal models used for r and omized clinical trials do not take into account the unique design features of SMART . We discuss modeling considerations for various forms of SMART design s , emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART . For illustration , we use data from three SMART case studies with increasing level of complexity , in autism , child attention deficit hyperactivity disorder , and adult alcoholism . In all three SMARTs , we illustrate how to accommo date the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated- measures outcome BACKGROUND There is an urgent need for the development of cost-effective preventive strategies to reduce the onset of mental disorders . AIMS To establish the cost-effectiveness of a stepped care preventive intervention for depression and anxiety disorders in older people at high risk of these conditions , compared with routine primary care . METHOD An economic evaluation was conducted alongside a pragmatic r and omised controlled trial ( IS RCT N26474556 ) . Consenting individuals presenting with subthreshold levels of depressive or anxiety symptoms were r and omly assigned to a preventive stepped care programme ( n = 86 ) or to routine primary care ( n = 84 ) . RESULTS The intervention was successful in halving the incidence rate of depression and anxiety at euro563 ( pound412 ) per recipient and euro4367 ( pound3196 ) per disorder-free year gained , compared with routine primary care . The latter would represent good value for money if the willingness to pay for a disorder-free year is at least euro5000 . CONCLUSIONS The prevention programme generated depression- and anxiety-free survival years in the older population at affordable cost OBJECTIVES To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury ; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs ; and to gain participants ' perspective on experiencing whiplash injury , NHS treatment , and recovery within the context of the Managing Injuries of the Neck Trial ( MINT ) . DESIGN Two linked , pragmatic , r and omised controlled trials . In Step 1 , emergency departments ( EDs ) were cluster r and omised to usual care advice ( UCA ) or The Whiplash Book advice (WBA)/active management advice . In Step 2 , participants were individually r and omised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions . An economic evaluation and qualitative study were run in parallel with the trial . SETTING Twelve NHS trusts in Engl and comprising 15 EDs . PARTICIPANTS People who attended EDs with an acute whiplash injury of whiplash-associated disorder grade s I-III were eligible for Step 1 . People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2 . INTERVENTIONS In Step 1 , the control intervention was UCA and the experimental intervention was a psycho-educational intervention ( WBA/active management advice ) . In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments . MAIN OUTCOME The primary outcome was the Neck Disability Index ( NDI ) , which measures severity and frequency of pain and symptoms , and a range of activities including self-care , driving , reading , sleeping and recreation . Secondary outcomes included the mental and physical health-related quality -of-life ( HRQoL ) subscales of the Short Form question naire-12 items ( SF-12 ) and the number of work days lost . RESULTS A total of 3851 patients were recruited to Step 1 of the trial . 1598 patients attending EDs were r and omised to UCA , and 2253 were r and omised to WBA/active management . Outcome data were obtained at 12 months for 70 % and 80 % of participants at Step 1 and Step 2 , respectively . The majority of people recovered from the injury . Eighteen per cent of the Step 1 cohort had late whiplash syndrome . There was no statistically or clinical ly significant difference observed in any of the outcomes for participants attending EDs r and omised to UCA or active management advice [ difference in NDI 0.5 , 95 % confidence interval ( CI ) -1.8 to 2.8 ] . In Step 2 the physiotherapy package result ed in improvements in neck disability at 4 months compared with a single advice session , but these effects were small at the population level ( difference in NDI -3.2 , 95 % CI -5.8 to -0.7 ) . The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up ( difference -40.2 , 95 % CI -44.3 to -35.8 ) . CONCLUSIONS MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries . A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session . However , from a health-care perspective , the physiotherapy package was not cost-effective at current levels of willingness to pay . Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life . However , an important benefit of the physiotherapy package was a reduction in work days lost ; consequently , the intervention may prove cost-effective at the societal level . TRIAL REGISTRATION Current Controlled Trials IS RCT N33302125 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 16 , No. 49 . See the HTA programme website for further project information Background : In a stepped-down approach , patients begin with a more intensive treatment and are stepped down to a less intensive treatment based on achieving treatment goals . This study compared a st and ard behavioural weight loss programme ( BWLP ) to a stepped-down approach to treatment . Methods : Fifty-two overweight/obese adults ( Age : M = 47 years , SD = 13.5 ; female = 67 % ) participated in an 18-week BWLP . Half of them were r and omly assigned to be stepped down from weekly group meetings based on completion of weight loss goals ( 3 % ) every 6 weeks , while the other half remained in their groups regardless of weight loss . Results : There was a significant difference favouring the BWLP in the proportion of participants who met or exceeded their 3 % weight loss goal during the first six weeks . While not statistically significant by the end of treatment , the BWLP participants lost nearly 3 % more body weight than stepped-down participants ( SC = 4.9 % vs. BWLP = 7.8 % ; p = .10 ) . Greater self-monitoring was associated with increased likelihood of stepped-care eligibility and higher percent weight loss at the end of treatment ( p < .01 ) . Conclusion : There was little evidence to support the efficacy of the stepped-down approach for behavioural weight loss treatment employed in this investigation OBJECTIVE This study tested the effect of beginning treatment with a speech-generating device ( SGD ) in the context of a blended , adaptive treatment design for improving spontaneous , communicative utterances in school-aged , minimally verbal children with autism . METHOD A total of 61 minimally verbal children with autism , aged 5 to 8 years , were r and omized to a blended developmental/behavioral intervention ( JASP+EMT ) with or without the augmentation of a SGD for 6 months with a 3-month follow-up . The intervention consisted of 2 stages . In stage 1 , all children received 2 sessions per week for 3 months . Stage 2 intervention was adapted ( by increased sessions or adding the SGD ) based on the child 's early response . The primary outcome was the total number of spontaneous communicative utterances ; secondary measures were the total number of novel words and total comments from a natural language sample . RESULTS Primary aim results found improvements in spontaneous communicative utterances , novel words , and comments that all favored the blended behavioral intervention that began by including an SGD ( JASP+EMT+SGD ) as opposed to spoken words alone ( JASP+EMT ) . Secondary aim results suggest that the adaptive intervention beginning with JASP+EMT+SGD and intensifying JASP+EMT+SGD for children who were slow responders led to better posttreatment outcomes . CONCLUSION Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel , blended intervention that focuses on joint engagement and play skills and incorporates an SGD . Future studies should further explore the tailoring design used in this study to better underst and children 's response to treatment . Clinical trial registration information-Developmental and Augmented Intervention for Facilitating Expressive Language ( CCNIA ) ; http:// clinical trials.gov/ ; NCT01013545 BACKGROUND The aim of this study was to evaluate the effectiveness of a stepped-care program to prevent the onset of depression and anxiety disorders in elderly people living in residential homes . METHODS A pragmatic r and omized controlled trial was conducted to compare the intervention with usual care in 14 residential homes in the Netherl and s. A total of 185 residents with a minimum score of 8 on the Centre for Epidemiologic Studies Depression Scale , who did not meet the diagnostic criteria for a depressive or anxiety disorder , and were not suffering from severe cognitive impairment , were recruited between April 2007 and December 2008 . They were r and omized to a stepped-care program ( N = 93 ) or to usual care ( N = 92 ) . The stepped-care participants sequentially underwent watchful waiting , a self-help intervention , life review , and a consultation with the general practitioner . The primary outcome measure was the incidence of a major depressive disorder ( MDD ) or anxiety disorder during a period of one year according to the Mini International Neuropsychiatric Interview . RESULTS The intervention was not effective in reducing the incidence of the combined outcome of depression and anxiety ( incidence rate ratio ( IRR ) = 0.50 ; 95 % confidence interval ( CI ) = 0.23 - 1.12 ) . However , the intervention was superior to usual care in reducing the risk of MDD incidence ( IRR = 0.26 ; 95 % CI = 0.12 - 0.80 ) contrary to anxiety incidence ( IRR = 1.32 ; 95 % CI = 0.48 - 3.62 ) . CONCLUSIONS These results suggest that the stepped-care program is effective in reducing the incidence of depression , but is not effective in preventing the onset of anxiety disorders in elderly people living in residential homes BACKGROUND Depression and anxiety are common in people with a chronic somatic disease . Although guidelines recommend stepped care , the effectiveness of this approach has not been evaluated in people with diabetes , asthma , or COPD in primary care . METHODS 3559 People were sent screening question naires ( 41 % response ) . Of 286 persons with anxiety and /or depression ( Generalized Anxiety Disorder question naire , GAD-7 , cut-off ≥ 8 and /or Patient Health Question naire , PHQ-9 , cut-off ≥ 7 ) , 46 were r and omized into the intervention ( stepped care and monitoring of symptoms ; n = 23 ) or control ( usual care ) group ( n = 23 ) . Main outcomes were symptoms of anxiety and depression after the 12-months intervention and six months post intervention . Analysis of covariance was first adjusted for condition and baseline GAD-7/PHQ-9 scores and additionally for age , sex and education . RESULTS The intervention group had a significantly lower level of anxiety symptoms at the end of the program ( GAD-7 6 ± 6 vs. 9 ± 6 ; Cohen 's d = 0.61 ) . This effect was still present six months post intervention . The effect on depression was statistically significant in the first model ( PHQ-9 6 ± 4 vs. 9 ± 6 ; p = 0.035 ) , but not in the fully adjusted model ( p = 0.099 ) , despite a large effect size ( d = 0.63 ) . At six months post intervention there was no statistically significant difference in symptoms of depression between the two groups although the difference in symptoms was still clinical ly significant ( Cohen 's d = 0.61 ) . LIMITATIONS Many people were screened , but relatively few participated in the r and omized controlled trial . CONCLUSIONS Stepped care with monitoring result ed in a lower level of symptoms of anxiety and depression in people with a chronic condition Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level . In a cluster-level dynamic treatment regimen , the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention , including aggregate measures of the individuals or patients that compose it . Cluster-r and omized sequential multiple assignment r and omized trials can be used to answer multiple open questions preventing scientists from developing high- quality cluster-level dynamic treatment regimens . In a cluster-r and omized sequential multiple assignment r and omized trial , sequential r and omizations occur at the cluster level and outcomes are observed at the individual level . This manuscript makes two contributions to the design and analysis of cluster-r and omized sequential multiple assignment r and omized trials . First , a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment r and omized trial . The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials . Second , sample size calculators are derived for two common cluster-r and omized sequential multiple assignment r and omized trial design s for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome . The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is , to our knowledge , the first-ever cluster-r and omized sequential multiple assignment r and omized trial in psychiatry 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 BACKGROUND To compare the effectiveness and cost of stepped care trauma-focused cognitive behavioral therapy ( SC-TF-CBT ) , a new service delivery method design ed to address treatment barriers , to st and ard TF-CBT among young children who were experiencing posttraumatic stress symptoms ( PTSS ) . METHODS A total of 53 children ( ages 3 - 7 years ) who were experiencing PTSS were r and omly assigned ( 2:1 ) to receive SC-TF-CBT or TF-CBT . Assessment s by a blinded evaluator occurred at screening/baseline , after Step One for SC-TF-CBT , posttreatment , and 3-month follow-up . TRIAL REGISTRATION Clinical Trials.gov : https://www . clinical trials.gov/ct2/show/NCT01603563 . RESULTS There were comparable improvements over time in PTSS and secondary outcomes in both conditions . Noninferiority of SC-TF-CBT compared to TF-CBT was supported for the primary outcome of PTSS , and the secondary outcomes of severity and internalizing symptoms , but not for externalizing symptoms . There were no statistical differences in comparisons of changes over time from pre- to posttreatment and pre- to 3-month follow-up for posttraumatic stress disorder diagnostic status , treatment response , or remission . Parent satisfaction was high for both conditions . Costs were 51.3 % lower for children in SC-TF-CBT compared to TF-CBT . CONCLUSIONS Although future research is needed , preliminary evidence suggests that SC-TF-CBT is comparable to TF-CBT , and delivery costs are significantly less than st and ard care . SC-TF-CBT may be a viable service delivery system to address treatment barriers OBJECTIVE To investigate predictors and moderators of treatment outcome by comparing immediate face-to-face cognitive behavioral therapy ( FtF-CBT ) to a Stepped Care treatment model comprising three steps : Psychoeducation , Internet-delivered CBT , and FtF-CBT for panic disorder ( PD ) and social anxiety disorder ( SAD ) . METHOD Patients ( N = 173 ) were recruited from nine public mental health out-patient clinics and r and omized to immediate FtF-CBT or Stepped Care treatment . Characteristics related to social functioning , impairment from the anxiety disorder , and comorbidity was investigated as predictors and moderators by treatment format and diagnosis in multiple regression analyses . RESULTS Lower social functioning , higher impairment from the anxiety disorder , and a comorbid cluster C personality disorder were associated with significantly less improvement , particularly among patients with PD . Furthermore , having a comorbid anxiety disorder was associated with a better treatment outcome among patients with PD but not patients with SAD . Patients with a comorbid depression had similar outcomes from the different treatments , but patients without comorbid depression had better outcomes from immediate FtF-CBT compared to guided self-help . CONCLUSIONS In general , the same patient characteristics appear to be associated with the treatment outcome for CBT provided in low- and high-intensity formats when treated in public mental health care clinics . The findings suggest that patients with lower social functioning and higher impairment from their anxiety disorder benefit less from these treatments and may require more adapted and extensive treatment . CLINICAL TRIALS.GOV : Identifier : NCT00619138 |
487 | 26,794,700 | No significant difference in CBL was found around submerged and nonsubmerged dental implants | STATEMENT OF PROBLEM To my knowledge , there is no systematic review of crestal bone loss ( CBL ) around submerged and nonsubmerged dental implants .
PURPOSE The purpose of this review was to systematic ally assess CBL around submerged and nonsubmerged dental implants .
MATERIAL AND METHODS The addressed focused question was , " Does crestal and subcrestal placement of dental implants influence crestal bone levels ? " | The purpose of this study was to evaluate crestal bone loss around 282 two-piece implants with straight ( n = 193 ) and platform-switched ( n = 89 ) abutment connections after placement at various crestal levels . Implants were assigned into two groups according to straight and platform-switched abutment connections . Each group was further subdivided into three groups depending on the location ( supracrestal , crestal , or subcrestal ) of the implant cervical platform . Linear measurements of bone resorption were made from the implant 's platform to the first point of bone-to-implant contact at the time of implant placement and 2 years postrestoration . Data were statistically analyzed . Statistically significant differences were found between subgroups in both straight and platform-switched categories . The only nonstatistically significant difference ( P = .341 ) arose when comparing the supra- and subcrestal locations in the straight abutment connection group . The platform-switched group exhibited significantly less bone loss ( P = .046 ) only in subcrestal locations . The platform-switched concept was not beneficial during the overall comparison , but it was for the subcrestal location of the abutment connection . Crestal placement of the implant-abutment connection result ed in higher marginal bone resorption in both straight and platform-switched abutments BACKGROUND The purpose of this study is to assess the influence of the placement level of implants with a laser-microtextured collar design on the outcomes of crestal bone and soft tissue levels . In addition , we assessed the vertical and horizontal defect fill and identified factors that influenced clinical outcomes of immediate implant placement . METHODS Twenty-four patients , each with a hopeless tooth ( anterior or premolar region ) , were recruited to receive dental implants . Patients were r and omly assigned to have the implant placed at the palatal crest or 1 mm subcrestally . Clinical parameters including the keratinized gingival ( KG ) width , KG thickness , horizontal defect depth ( HDD ) , facial and interproximal marginal bone levels ( MBLs ) , facial threads exposed , tissue-implant horizontal distance , gingival index ( GI ) , and plaque index ( PI ) were assessed at baseline and 4 months after surgery . In addition , soft tissue profile measurements including the papilla index , papilla height ( PH ) , and gingival level ( GL ) were assessed after crown placement at 6 and 12 months post-surgery . RESULTS The overall 4-month implant success rate was 95.8 % ( one implant failed ) . A total of 20 of 24 patients completed the study . At baseline , there were no significant differences between crestal and subcrestal groups in all clinical parameters except for the facial MBL ( P = 0.035 ) . At 4 months , the subcrestal group had significantly more tissue thickness gain ( keratinized tissue ) than the crestal group compared to baseline . Other clinical parameters ( papilla index , PH , GL , PI , and GI ) showed no significant differences between groups at any time . A facial plate thickness ≤1.5 mm and HDD ≥2 mm were strongly correlated with the facial marginal bone loss . A facial plate thickness ≤2 mm and HDD ≥3 were strongly correlated with horizontal dimensional changes . CONCLUSIONS The use of immediate implants was a predictable surgical approach ( 96 % survival rate ) , and the level of placement did not influence horizontal and vertical bone and soft tissue changes . This study suggests that a thick facial plate , small gaps , and premolar sites were more favorable for successful implant clinical outcomes in immediate implant placement The medium-long term success of osseointegrated dental implants is evaluated on the basis of the degree of osseointegration over time , assessed by radiographic or instrumental analysis ( ISQ ) . Over the years , the question has always been which surgical technique can provide a better performance in the medium-long term and , thanks to literature studies , it has been evidence d that there are no differences between " one stage " and " two stage " interventions . The purpose of this study is to evaluate clinical and radiographic parameters , referring to interventions for the insertion of dental implants characterized by a new kind of implant surface ( Synthegra ® GEASS , Udine ) . The prospect i ve study , not r and omized and controlled , referred to the insertion of 18 implants on 9 patients with mono or bilateral edentulism , with measurements at 1 , 3 , 6 and 12 months and an overall follow-up at 3 years , in order to evaluate the different degree of crestal bone resorption using the submerged and transmucosal surgical technique . The results of our study show that there are no differences in the resorption of the two surgical techniques , with an average bone resorption of 2,05±0,16 mm , comparable with values reported in literature BACKGROUND It has been reported in many articles that marginal bone resorptions are prevented by platform-switching design . However , what occurs when these implants are placed in the apical position is not completely known . PURPOSE This report describes a r and omized controlled clinical trial study that aims to test the hypothesis that less resorption will occur when platform-switching implants are placed 1 mm below bone level . MATERIAL S AND METHODS A total of 56 r and omly selected implants were inserted bilaterally , either 1 mm below bone level ( test group , 28 implants ) or at bone level ( control group , 28 implants ) of the patients ' posterior regions . Marginal bone resorptions were examined through periapical radiographies taken with the parallel technique at the time of crown cementation and the third , sixth , 12th , and 36th months after prosthetic loading . The modified plaque index , gingival index , bleeding on probing , and probing depths were used for follow-up periodontal care of the implants . RESULTS After 3 years , the mean radiographic vertical bone loss in the control group was significantly lower than in the test group ( 0.56 ± 0.35 mm and 1.21 ± 1.05 mm , respectively ) ( p < .01 ) . In terms of periodontal indexes , there were no statistically significant differences between the two groups ( p > .05 ) . No peri-implantitis or peri-implant mucositis was observed around the test or control implants . CONCLUSIONS More marginal bone resorptions occurred after the third year of loading in implants placed 1 mm below bone level . However , the resorptions did not reach the implants thread . In the control group , the first bone implant contact was placed under the level of the first threads . Therefore , the present r and omized clinical trial confirmed the hypothesis that placing platform-switching implants 1 mm below bone level reduced marginal bone loss . It can be noted that to reduce resorption , platform-switching implants should be placed below bone level OBJECTIVES To assess the impact of microgrooved abutments and the insertion depth on crestal bone changes at titanium implants with platform switch . MATERIAL S AND METHODS A total of n = 3 titanium implants ( conical abutment connection ) were inserted in each hemim and ible of n = 6 foxhounds with the implant shoulder ( IS ) located at either epicrestal , supracrestal ( + 1 mm ) , or subcrestal ( -1 mm ) positions and r and omly ( split-mouth design ) connected with machined or partially microgrooved healing abutments . At 20 weeks , tissue biopsies were processed for histological ( primary outcome : net bone loss - NET ) analyses . RESULTS Subcrestal positioning of IS tended to be associated with higher mean NET values ( mm ) at both machined ( subcrestal [ -0.72 ± 0.32 ] > epicrestal [ -0.34 ± 0.21 ] > supracrestal [ + 0.20 ± 0.64 ] ) and microgrooved ( subcrestal [ -0.48 ± 0.25 ] > epicrestal [ -0.13 ± 0.54 ] > supracrestal [ + 0.33 ± 0.58 ] ) abutments . However , these differences failed to reach statistical significance . CONCLUSIONS The insertion depth may have a direct influence on crestal bone-level changes at both types of abutments investigated OBJECTIVE This prospect i ve r and omized match-paired controlled trial aim ed to evaluate the impact of implant platform diameter on marginal bone level around implants restored according to the platform switching ( PS ) concept . MATERIAL AND METHODS A total of 24 implants were examined in 12 patients . All patients received two adjacent implants inserted at the crestal level : 4.3 mm ( control group ) and 4.8 mm ( test group ) in diameter . Mesio-distal implant position was r and omly performed . According to the PS concept , for restoration , a 3.8 and 4.3 mm diameter abutment was used , respectively in the control and test groups , result ing , in both groups , with 0.25 mm of implant/abutment mismatching . Implant restorations were splinted . Eighteen months after final restoration , periapical st and ardized digital radiographs were taken to evaluate marginal bone level alterations after loading . The Wilcoxon Signed-Rank Test was selected to identify differences between groups . RESULTS At the last follow-up , control implants exhibited a mean bone loss value of 1.10 mm ( SD : 0.47 mm ) ; the test group showed a mean value of 1.09 mm ( SD : 0.08 mm ) . No statistically significant differences were found between test and control groups . CONCLUSIONS Within the limits of this study , the present results suggest that bone resorption is mostly related to biologic ( biologic width re-establishment ) rather than to biomechanical factors ( implant platform diameter ) . Furthermore long-term studies with a wider sample size are needed to confirm the platform diameter influence on hard tissue response around implants restored according to the PS concept PURPOSE Submerged and nonsubmerged ITI solid-screw titanium implants were followed retrospectively from 1989 to 1993 and prospect ively from 1994 on to analyze long-term prognosis in partially and fully edentulous patients . MATERIAL AND METHODS A total of 468 implants were consecutively inserted in 191 patients from 1989 to 1998 . Two hundred twenty-eight successfully integrated fixed-restoration implants and 238 with removable restorations were restored following a healing period of 4 to 6 months ( 9 months in sinus floor elevation sites ) . From 1994 on all implants inserted were documented annually up to 9 years . During examination the clinical status of the implants was analyzed and evaluated according to predefined criteria of success and this allowed the calculation of 10-year cumulative survival and success rates for 468 implants . RESULTS Two implants ( 0.43 % ) did not successfully integrate during the healing period , and 8 implants ( 1.7 % ) were classified as failures during follow-up ( 1 late failure under load , 7 with a progressive bone loss from 1 to 3 threads ) . Including 68 implants in subjects who dropped out ( with a dropout rate of 14.4 % ) , the 10-year cumulative survival and success rates were 99.2 % and 96.4 % , respectively . DISCUSSION Over the course of this long-term study , osseointegrated implants , once used as a last possible solution , became nearly st and ard in cases of single-tooth implants because of the high rate of long-term success . Life table analysis not only determines whether an implant is functioning , it also makes a statement about its clinical status according to strict success criteria . CONCLUSION The study demonstrated that ITI solid-screw titanium implants achieved success rates above 95 % in a clinical center for an observation period of up to 10 years BACKGROUND Today , implants are placed using both non-submerged and submerged approaches , and in 1- and 2-piece configurations . Previous work has demonstrated that peri-implant crestal bone reactions differ radiographically under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of the interface ( microgap ) between the implant and abutment/restoration in 2-piece configurations . The purpose of this investigation was to examine histometrically crestal bone changes around unloaded non-submerged and submerged 1- and 2-piece titanium implants in a side-by-side comparison . METHODS A total of 59 titanium implants were r and omly placed in edentulous m and ibular areas of 5 foxhounds , forming 6 different implant subgroups ( types A-F ) . In general , all implants had a relatively smooth , machined coronal portion as well as a rough , s and blasted and acid-etched ( SLA ) apical portion . Implant types A-C were placed in a non-submerged approach , while types D-F were inserted in a submerged fashion . Type A and B implants were 1-piece implants with the rough/smooth border ( r/s ) at the alveolar crest ( type A ) or 1.0 mm below ( type B ) . Type C implants had an abutment placed at the time of surgery with the interface located at the bone crest level . In the submerged group , types D-F , the interface was located either at the bone crest level ( type D ) , 1 mm above ( type E ) , or 1 mm below ( type F ) . Three months after implant placement , abutment connection was performed in the submerged implant groups . At 6 months , all animals were sacrificed . Non-decalcified histology was analyzed by evaluating peri-implant crestal bone levels . RESULTS For types A and B , mean crestal bone levels were located adjacent ( within 0.20 mm ) to the rough/smooth border ( r/s ) . For type C implants , the mean distance ( + /- st and ard deviation ) between the interface and the crestal bone level was 1.68 mm ( + /- 0.19 mm ) with an r/s border to first bone-to-implant contact ( fBIC ) of 0.39 mm ( + /- 0.23 mm ) ; for type D , 1.57 mm ( + /- 0.22 mm ) with an r/s border to fBIC of 0.28 mm ( + /- 0.21 mm ) ; for type E , 2.64 mm ( + /- 0.24 mm ) with an r/s border to fBIC of 0.06 mm ( + /- 0.27 mm ) ; and for type F , 1.25 mm ( + /- 0.40 mm ) with an r/s border to fBIC of 0.89 mm ( + /- 0.41 mm ) . CONCLUSIONS The location of a rough/smooth border on the surface of non-submerged 1-piece implants placed at the bone crest level or 1 mm below , respectively , determines the level of the fBIC . In all 2-piece implants , however , the location of the interface ( microgap ) , when located at or below the alveolar crest , determines the amount of crestal bone resorption . If the same interface is located 1 mm coronal to the alveolar crest , the fBIC is located at the r/s border . These findings , as evaluated by non-decalcified histology under unloaded conditions , demonstrate that crestal bone changes occur during the early phase of healing after implant placement . Furthermore , these changes are dependent on the surface characteristics of the implant and the presence/absence as well as the location of an interface ( microgap ) . Crestal bone changes were not dependent on the surgical technique ( submerged or non-submerged ) PURPOSE The aim of the present study was to evaluate bone-to-implant contact ( BIC ) and bone remodeling dynamics after immediate implant placement at different levels in relation to the crestal bone with two different implant design s in beagle dogs . MATERIAL S AND METHODS The m and ibular second , third and fourth premolars of six beagle dogs were extracted bilaterally and three implants were immediately placed in the hemi-arches of each dog . R and omly , three cylindrical and three tapered implants were inserted crestally ( control group ) or 2 mm subcrestally ( test group ) . Both groups were treated with a minimal mucoperiosteal flap elevation approach . A gap from the buccal cortical wall to the implant was always left . Three dogs were allowed a 4-week submerged healing period and the other three an 8-week submerged healing period . The animals were sacrificed and sample s were obtained . Biopsies were processed for ground sectioning . Histomorphometric analysis was carried out in order to compare BIC , de novo bone formation and bone remodeling . RESULTS All implants osseointegrated clinical ly and histologically . Healing patterns examined microscopically at 4 and 8 weeks for both groups ( crestal and subcrestal ) yielded similar qualitative bone findings . The total BIC mean value for the crestal group was 36.48 ± 3.4 % and for the subcrestal group was 41.46 ± 4.2 % . The mean percentage of newly formed BIC was greater with the cylindrical implant design ( 46.06 ± 1.09 % ) than with the tapered design ( 33.89 ± 1.72 % ) . There was less bone resorption in the subcrestal group ( test ) than crestal group ( control ) . CONCLUSION These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri-implant tissue remodeling . However , less resorption of the lingual crest may be expected when implants are placed 2 mm subcrestally . Moreover , higher BIC values were found in cylindrical implants placed subcrestally PURPOSE The aim of the present study was to evaluate bone remodeling and bone-to-implant contact ( BIC ) after immediate placement at different levels in relation to the crestal bone of Beagle dogs . MATERIAL S AND METHODS The m and ibular bilateral second , third and fourth premolars of six Beagle dogs were extracted and six implants were immediately placed in the hemi-arches of each dog . R and omly , three cylindrical and three tapered implants were inserted crestally ( control group ) and 2 mm subcrestally ( experimental group ) . Both groups were treated with a minimal mucoperiosteal flap elevation approach . A gap from the buccal cortical wall to the implant was always left . Three dogs were allowed a 4-week submerged healing period and the other three an 8-week submerged healing period . The animals were sacrificed and biopsies were obtained . Biopsies were processed for ground sectioning . Histomorphometric analysis was carried out in order to compare buccal and lingual bone height loss , and BIC between the two groups . RESULTS All implants osseointegrated clinical ly and histologically . Healing patterns examined microscopically at 4 and 8 weeks for both groups ( crestal and subcrestal ) yielded similar qualitative bone findings . The distance from the top of the implant collar to the first BIC in the lingual crest ( A-Lc ) showed a significant difference ( P=0.0313 ) : 1.91 ± 0.2 mm in the control group and 1.08 ± 0.2 mm in the experimental group . There was less bone resorption in subcrestal implants than crestal implants . The mean percentage of newly formed BIC was greater with the cylindrical implant design ( 46.06 ± 4.09 % ) than with the tapered design ( 32.64 ± 3.72 % ) . CONCLUSION These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri-implant tissue remodeling . However , less resorption of the Lc may be expected when implants are placed 2 mm subcrestally OBJECTIVE The aim of this study was to evaluate the buccal bone plate remodeling after immediate implantation using the flapless approach with or without bone graft into the gap between the implant and the buccal bone . MATERIAL AND METHODS Eight dogs had the m and ibular bicuspids extracted without flaps , and four implants were installed on each side , totaling eight implants per animal . R and omly , in one side , the implants were positioned at the bone crest level ( equicrestal ) , and on the opposite side , the implants were positioned 2 mm subcrestal . All the implants were positioned 2.0 mm from the buccal bone plate ( gap ) and associated or not with grafting material . Therefore , the following treatments were performed : implants subcrestal test ( SCTG ) with bone graft and control ( SCCG ) without bone graft , and equicrestal test ( ECTG ) with bone graft and control ( ECCG ) without bone graft . One week following the surgeries , metallic prostheses were installed . Bone markers were administered 1 , 2 , 4 , and 12 weeks after implant placement for fluorescence analysis . Ground sections were prepared from 12-week healing biopsies , and histomorphometry was performed . RESULTS The histomorphometric evaluation presents significant better results for the ECTG in the vertical crestal bone resorption , but the other parameters showed better results for the SCCG . The fluorescence evaluation in adjacent areas showed numerically different results between groups with a small decrease at 12 weeks , except for the SCCG , which was higher at this time . The distant area showed a continuous increase in the marked bone . CONCLUSION The equicrestally placed implants presented little or no loss of the buccal bone wall . The subcrestally positioned implants presented loss of buccal bone , regardless of the use of bone graft . However , the buccal bone was always coronal to the implant shoulder . Both the equicrestal and subcrestal groups were benefited in the early stages of bone healing as evidence d by the fluorescence analysis A multicenter clinical study of dental implants is being conducted by the Dental Implant Clinical Research Group to investigate the influence of implant design , application , and site on clinical performance and crestal bone . This article reports on the percentage of success up to implant uncovering for different implant design s and the distribution of failures across study sites . Data from 2,847 implants placed at 32 study sites were analyzed . Percentages of success up to implant uncovering were calculated for study implants overall , by implant design , by implant design within study strata , and according to individual study sites and quartile groupings of sites based on success . Comparisons were made , with chi-square and exact tests employed where appropriate . Differences were found between the different implant design s for the study overall , and between implant design s within the different study strata . Although some implant design s were found to have generally high success across study sites , some study sites design ated as having surgeons with less experience tended to have higher failure levels , and one implant design failed at higher rates in a subset of study sites . The percentage and distribution of implant failures varied across study sites and by implant design . These differences appeared to be in part related to the level of experience of the surgeons . Further investigation should focus on identification of factors that contribute to higher success in implant placement with different implant design PURPOSE / AIM Evaluate differences in bone remodeling , soft tissue reactions and biological width formation around immediate implants placed at different level in relation to the crestal bone in beagle dogs . MATERIAL AND METHODS The m and ibular second , third and fourth premolars of six beagle dogs were extracted , and three implants were placed in the right side of each dog . Healing abutments were adjusted ( n = 18 ) . After 4 weeks , the procedure was repeated on the left side of the m and ible ( n = 18 ) . R and omly , three implants were placed at crestal level ( control group ) , and three implants were placed 2 mm subcrestally ( test group ) in relation to the crestal bone in each animal . The dogs were sacrificed after 8 weeks from the first surgical procedure , and biopsies were obtained . Sample s were processed for ground sectioning . Histometric analysis was carried out to compare buccal and lingual bone resorption , soft tissue behavior and biological width formation in both groups . RESULTS Crestal bone resorption was higher in the test group when considering the difference of 2 mms ( IS-B = 2.05 ± 0.36 mm , control ; 1.75 ( + 2 ) ± 0.38 mm , test ) . However , the dimensions of the biological width were similar for both groups ( PM-C = 3.34 ± 0.53 mm , control ; 3.13 ± 0.55 mm , test ) . CONCLUSIONS The alterations that occurred in the peri-implant soft tissues may be related to the hard tissue remodeling , showing similar quantitative findings in the biological width formation in both groups . Even though the subcrestal placement might reduce the distance from the implant shoulder to the first bone-to-implant contact and reestablish the biological width dimension in a most coronal position , it might not have any effect on minimizing the marginal bone loss PURPOSE The aim of this clinical trial was to evaluate the influence of gingival tissue thickness on crestal bone loss around dental implants after a 1-year follow-up . MATERIAL S AND METHODS Forty-six implants ( 23 test and 23 control ) were placed in 19 patients . The test implants were placed about 2 mm supracrestally , whereas the control implants were positioned at the bone level . Before implant placement , the tissue thickness at implant sites was measured with a periodontal probe . After healing , metal-ceramic cement-retained prostheses were constructed . According to tissue thickness , the test implants were divided into A ( thin ) and B ( thick ) groups . Intraoral radiographs were performed and crestal bone changes were measured at implant placement and after 1 year . RESULTS Mean bone loss around the test implants in group A ( thin mucosa ) was 1.61 + /- 0.24 mm ( SE ; range , 0.9 to 3.3 mm ) on the mesial and 1.28 + /- 0.167 mm ( range , 0.8 to 2.1 mm ) on the distal . Mean bone loss in test group B ( thick mucosa ) implants was 0.26 + /- 0.08 mm ( range , 0.2 to 0.9 mm ) on the mesial aspect and 0.09 + /- 0.05 mm ( range , 0.2 to 0.6 mm ) on the distal aspect . Mean bone loss around control implants was 1.8 + /- 0.164 mm ( range , 0.6 to 4.0 mm ) and 1.87 + /- 0.166 mm ( range , 0.0 to 4.1 mm ) on the mesial and distal aspects , respectively . Analysis of variance revealed a significant difference in terms of bone loss between test A ( thin ) and B ( thick ) groups on both the mesial and the distal . CONCLUSION Initial gingival tissue thickness at the crest may be considered as a significant influence on marginal bone stability around implants . If the tissue thickness is 2.0 mm or less , crestal bone loss up to 1.45 mm may occur , despite a supracrestal position of the implant-abutment interface OBJECTIVES The aim of the present study was to compare crestal bone loss with different implant design s inserted immediately in crestal or subcrestal position in post- extraction sockets in a dog model . MATERIAL S AND METHODS The m and ibular second , third , fourth premolars , and the first molars of six adult fox hound dogs were extracted bilaterally , and 48 implants were placed immediately in both hemi-arches of each dog . R and omly , eight implants ( sky classic ( ® ) and blue sky ( ® ) ) were inserted , four crestally ( control group ) and four 2 mm subcrestally ( test group ) . Both groups were treated with a minimal mucoperiosteal flap elevation approach . After a 12-week healing period , the animals were sacrificed , and sample s were obtained . Biopsies were processed for ground sectioning . Histomorphometric analysis was carried out to compare buccal and lingual bone height loss . RESULTS All implants were clinical ly and histologically osseointegrated . Healing patterns examined microscopically at eight and 12 weeks for both groups ( crestal and subcrestal ) yielded similar qualitative bone findings . At 12 weeks , the distance from the top of the implant collar to the first BIC ( ISBc ) showed significant difference between implant positions ( crestal or subcrestal ) in the buccal aspect ( P = 0.1253 ) , values for the crestal group being higher ( 1.79 ± 0.3 mm ) in comparison with the subcrestal group ( 0.89 ± 0.5 mm ) . Better results were achieved by both implant design s when implants were placed in the deeper position . No significant differences were found in BIC values ( P > 0.05 ) . The total BIC at 8 weeks was ( 46.22 ± 4.29 % ) for the crestal group and ( 49.72 ± 2.21 % ) for the subcrestal group ; at 12 weeks , it was ( 41.54 ± 3.87 % ) for the crestal group and ( 56.87 ± 3.46 % ) for the subcrestal group . CONCLUSIONS Within the limitations of this study , the findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri-implant tissue remodeling . However , less resorption of the lingual and buccal crest may be expected when implants are placed 2 mm subcrestally , but this is not related to implant design . Moreover , implants placed subcrestally produced better bone-to-implant contact measurements OBJECTIVE To evaluate bone-level alterations that occurred at implants of the Astra Tech(R ) System that were placed in the load carrying , posterior parts of the dentition using either a submerged ( two-stage ) or a non-submerged ( one-stage ) installation protocol . MATERIAL AND METHODS Eighty-four patients that required 115 fixed partial dentures ( FPDs or cases ) entered the prospect i ve study . All subjects were assigned one patient and > or = one case numbers . For the r and omization of cases , a custom-made program based on balanced r and om permuted blocks was utilized . The cases were assigned to two treatment groups , namely one-stage installation procedure , non-submerged technique ( group A ) and two-stage installation procedure , submerged technique ( group B ) . Several subjects contributed with cases to both groups A and B. Periodontal , endodontal and open caries lesions were treated prior to implant installation . All patients received careful oral hygiene instruction and training in self-performed plaque control measures . The surgical technique used for fixture installation followed the outline described in the manual for the Astra Tech System . The FPDs were placed 3 months ( m and ible ) and 6 months ( maxilla ) following implant installation . Immediately following FPD placement , a baseline examination was performed that included assessment of plaque , soft-tissue inflammation and bone level . Clinicians who were otherwise not involved in the study performed the radiographic measurements . Clinical and radiographical examinations were repeated once a year after the baseline examination . DATA ANALYSIS The primary outcome variable was the change in the bone level at the implants from the time of placement of the bridge ( FPD ) to the 1- and 2-year reexaminations . Fisher 's permutation test was used to test if differences existed between groups A and B , and between patients ( men/women , smokers/non-smokers , age ) , sites ( maxilla/m and ible ) and implants ( length , diameter ) . Pitman 's test was used to study correlations between bone shape and quality data and different radiographic bone-level data . RESULTS It was demonstrated that tissue healing following implant installation appeared to be independent of the surgical protocol , i.e. whether the marginal portions of the implants during surgery were fully or only partly submerged under the ridge mucosa . Thus , ( i ) in both treatment groups the number of implants that failed to osseointegrate ( early failures ) was small ( < 2 % ) ; ( ii ) at the end of the recommended periods of bone healing prior to loading , - in both groups , maxilla=6 months and m and ible=3 months - the level of the marginal bone was close to the coronal rim of the fixture ; group A : 1.54+/-0.92 mm , group B : 1.31+/-0.77 mm . The current study also demonstrated that irrespective of surgical protocol ( two-stage , one-stage ) , implants supporting the FPDs exhibited only small amount of radiographic bone loss during the first year of function ( group A : 0.02+/-038 mm , group B : 0.17+/-0.64 mm ) . Moreover , during the second year of function , the amount of additional bone loss that occurred in the two treatment groups was close to zero . CONCLUSION Periimplant bone-level change during function seemed to be unrelated to whether initial soft- and hard-tissue healing following implant installation had occurred under submerged or non-submerged conditions BACKGROUND The rehabilitation of the oral cavity with dental implants has become a predictable treatment modality . However , there have been only a few direct comparisons evaluating the submerged and nonsubmerged placement techniques . The purpose of this study was to characterize radiographic peri-implant bone changes following the insertion of submerged and nonsubmerged implants in the beagle dog . METHODS At the end of the extraction healing phase , 19 submerged and 19 nonsubmerged implants were r and omly placed in a split-mouth study design and observed over an 18-week period . For submerged implants , a second stage surgery and transmucosal abutment attachment was performed at week 12 . St and ardized dental radiographs taken at baseline , week 12 , and week 18 were used to measure peri-implant bone changes . The radiographs were analyzed with a simple computer assisted method . RESULTS A total of 43 st and ardized radiographs were exposed to evaluate the 38 implants . During the study period , all submerged and nonsubmerged implants demonstrated peri-implant bone loss . At baseline , both submerged and nonsubmerged implants had similar bone levels ( P > or = 0.05 ) . When the mean peri-implant bone levels for submerged and nonsubmerged implants were compared from baseline to week 12 , nonsubmerged implants had a significantly greater amount and rate of bone resorption than submerged implants ( P < or = 0.05 ) . Following week 12 , the initially submerged implant had a significantly higher rate and amount of peri-implant bone loss than the nonsubmerged implants ( P < or = 0.05 ) . However , by the end of the study period , week 18 , both submerged and nonsubmerged implants had comparable bone levels ( P > or = 0.05 ) . CONCLUSIONS The study indicates that , although the temporal patterns of peri-implant bone resorption differed , there were no differences between submerged and nonsubmerged implants in the overall amount and rate of peri-implant bone loss BACKGROUND It has been shown that thin mucosal tissues may be an important factor in crestal bone loss etiology . Thus , it is possible that mucosal tissue thickening with allogenic membrane might reduce crestal bone loss . PURPOSE The purpose of this study was to evaluate how implants with traditional connection maintain crestal bone level after soft tissue thickening with allogenic membrane . MATERIAL S AND METHODS One hundred three patients received 103 internal hex implants of 4.6 mm diameter with regular connection . According to gingiva thickness , patients were assigned into A ( thin tissues , n = 34 ) , B ( thin , thickened with allogenic membrane , n = 35 ) , and C group ( thick tissues , n = 34 ) . Groups A and C had one-stage approach , and in group B , implants were placed in two stages . Radiographic examination was performed after implant placement , 2 months after healing , after restoration , and after 1-year follow-up . Crestal bone loss was calculated medially and distally . Significance was set to 0.05 . RESULTS After 1-year follow-up , implants in group A had 1.65 ± 0.08-mm bone loss mesially and 1.81 ± 0.06 mm distally . Group B had 0.31 ± 0.05 mm mesially and 0.34 ± 0.05 mm distally . C group implants experienced bone loss of 0.44 ± 0.06 mm mesially and 0.47 ± 0.07 mm distally . Differences between A and B , and A and C were significant ( p = .000 ) both mesially and distally , whereas differences between B and C were not significant mesially ( p = .166 ) and distally ( p = .255 ) . CONCLUSIONS It can be concluded that thin mucosal tissues may cause early crestal bone loss , but their thickening with allogenic membrane may significantly reduce bone resorption . Implants in naturally thick soft tissues experienced minor bone remodeling OBJECTIVE To determine if longitudinal bone level change at Astra Tech implants placed in the posterior part of the dentition was influenced by the healing conditions provided following implant placement , i.e. , submerged or non-submerged healing . MATERIAL AND METHODS Eighty-four patients and 115 fixed partial dentures ( FPDs or cases ) entered the study . The cases were r and omized into two implant installation groups : initially non-submerged ( group A ) or initially submerged ( group B ) implants . Three hundred and twenty-four implants were installed ( group A=153 ; group B=171 ) : 145 in the maxilla and 179 in the m and ible . Radiographs from the implant sites were obtained at FPD insertion ( baseline ) and subsequently every 12 months . In the radiographs , the position of the marginal bone at the mesial and distal aspects of the implants was determined and the radiographic ( Rx ) bone level change over time was calculated . RESULTS Seven implants failed to integrate ( four in group A and three in group B ) . During the 5 years of monitoring , three implants had to be removed and 35 implants were lost to follow-up . The Rx bone level alteration that occurred during year 1 was 0.02+/-0.38 mm in group A and 0.17+/-0.51 mm in group B. During the subsequent 4 years there was some further Rx bone loss in group B ( 0.02+/-0.62 mm ) , while in group A there was some gain of bone ( 0.07+/-0.5 mm ) . CONCLUSION The peri-implant bone level change and number of biological complications that took place during the 5 years was small and unrelated to the surgical protocol used for implant placement |
488 | 25,765,470 | There is strong evidence that antenatal distress during the pregnancy increases the likelihood of preterm birth .
CONCLUSION Complex paths of significant interactions between depression , anxiety and stress , risk factors and preterm birth were indicated in both direct and indirect ways .
The effects of pregnancy distress were associated with spontaneous but not with medically indicated preterm birth . | BACKGROUND Experiencing psychological distress such as depression , anxiety , and /or perceived stress during pregnancy may increase the risk for adverse birth outcomes , including preterm birth .
Clarifying the association between exposure and outcome may improve the underst and ing of risk factors for prematurity and guide future clinical and research practice s. AIM The aims of the present review were to outline the evidence on the risk of preterm associated with antenatal depression , anxiety , and stress . | BACKGROUND The goal of our study was to measure the effectiveness of a home-based intervention for prevention of low birth weight with 154 high-risk , low-income black women attending a prenatal clinic in Clevel and . METHODS Based on previous research , risk was defined by clinic registration between the 17th and 28th weeks of gestation , low family functioning score , and experience of at least one stressful life event prior to registration . Optional factors included being a smoker , a low maternal weight-height ratio , being age 27 or older , and a previous premature birth . A 21-item family function screen previously vali date d in a similar population was the primary determinant of psychosocial risk . Low birth weight was defined as weight less than 2,500 g regardless of gestational age . RESULTS There was no decrease in the rate of low birth weight for women who received four home visits focusing on smoking , drug and nutrition education , support , and links with community services , compared to women who received no visits . The number of prenatal visits was significantly higher in the intervention group , but an increased number of prenatal visits did not correlate with a reduced rate of low birth weight . Despite previous research , the family function screen was not an effective predictor of low birth weight in our study . A revised equation involving a history of previous premature birth , smoking , and a low maternal weight-height ratio did predict low birth weight . CONCLUSIONS These findings question the utility of short-term psychosocial interventions for influencing low birth-weight rates in low-income black clinic population s. The family function screen was not cross vali date d. Integration of any psychosocial intervention with the routine prenatal care occurring in the obstetrical clinic is suggested for future research The authors investigated a large number of stressors and measures of psychological distress in a multicenter , prospect i ve cohort study of spontaneous preterm birth among 5,337 Montreal (Canada)-area women who delivered from October 1999 to April 2004 . In addition , a nested case-control analysis ( 207 cases , 444 controls ) was used to explore potential biologic pathways by analyzing maternal plasma corticotrophin-releasing hormone ( CRH ) , placental histopathology , and ( in a subset ) maternal hair cortisol . Among the large number of stress and distress measures studied , only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth ( for values above the median , adjusted odds ratio = 1.8 ( 95 % confidence interval : 1.3 , 2.4 ) ) , with a dose-response relation across quartiles . The maternal plasma CRH concentration was significantly higher in cases than in controls in crude analyses but not after adjustment ( for concentrations above the median , adjusted odds ratio = 1.1 ( 95 % confidence interval : 0.8 , 1.6 ) ) . In the subgroup ( n = 117 ) of participants with a sufficient maternal hair sample , hair cortisol was positively associated with gestational age . Neither maternal plasma CRH , hair cortisol , nor placental histopathologic features of infection/inflammation , infa rct ion , or maternal vasculopathy were significantly associated with pregnancy-related anxiety or any other stress or distress measure . The biologic pathways underlying stress-induced preterm birth remain poorly understood This study investigates the relationship between adverse pregnancy outcomes in high-risk African American women in Washington , DC and sociodemographic risk factors , behavioral risk factors , and the most common and interrelated medical conditions occurring during pregnancy : diabetes , hypertension , preeclampsia , and Body Mass Index ( BMI ) . Data are from a r and omized controlled trial conducted in 6 prenatal clinics . Women in their 1st or 2nd trimester were screened for behavioral risks ( smoking , environmental tobacco smoke exposure , depression , and intimate partner violence ) and demographic eligibility . 1,044 were eligible , interviewed and followed through their pregnancies . Classification and Regression Trees ( CART ) methodology was used to : ( 1 ) explore the relationship between medical and behavioral risks ( reported at enrollment ) , sociodemographic factors and pregnancy outcomes ; ( 2 ) identify the relative importance of various predictors of adverse pregnancy outcomes ; and ( 3 ) characterize women at the highest risk of poor pregnancy outcomes . The strongest predictors of poor outcomes were prepregnancy BMI , preconceptional diabetes , employment status , intimate partner violence , and depression . In CART analysis , preeclampsia was the first splitter for low birthweight ; preconceptional diabetes was the first splitter for preterm birth ( PTB ) and neonatal intensive care admission ; BMI was the first splitter for very PTB , large for gestational age , Cesarean section and perinatal death ; employment was the first splitter for miscarriage . Preconceptional factors strongly influence pregnancy outcomes . For many of these women , the high risks they brought into pregnancy were more likely to impact their pregnancy outcomes than events during pregnancy Prenatal psychosocial predictors of infant birth weight and length of gestation were investigated in a prospect i ve study of 120 Hispanic and 110 White pregnant women . Hypotheses specifying that personal re sources ( mastery , self-esteem , optimism ) , prenatal stress ( state and pregnancy anxiety ) , and sociocultural factors ( income , education , ethnicity ) would have different effects on birth outcomes were tested using structural equation modeling . Results confirmed that women with stronger re sources had higher birth weight babies ( beta = .21 ) , whereas those reporting more stress had shorter gestations ( beta = -.20 ) . Re sources were also associated with lower stress ( beta = -.67 ) , being married , being White , having higher income and education , and giving birth for the first time . There was no evidence that re sources buffered the effects of stress . The importance of personal re sources in pregnancy is highlighted along with implication s for underst and ing the etiology of adverse birth outcomes Background : The aim of our study was to evaluate how sociodemographic factors , psychosocial adaptation to pregnancy and well-being levels are associated with the onset of preterm uterine contractions allowing symptomatic preterm labor . Methods : In a prospect i ve case-control design , 51 consecutive women admitted for threatened preterm labor were enrolled . The patients received st and ard care . The day before discharge , once contractions had been stopped , the patients were administered 2 question naires : the Prenatal Self-Evaluation Question naire of Lederman and the Psychological Well-Being Scales . Controls were enrolled among asymptomatic , healthy women attending routine prenatal care . They were matched for parity and gestational age . Results : Gestational age at inclusion ranged from 25 to 34 weeks . Fourteen cases and 4 controls delivered preterm . Cases were less educated than controls , showed a lower acceptance of pregnancy and worse relationship with others , namely with the husb and , compared to controls . They also displayed a reduced environmental mastery . Conclusion : Having a low education , poor relationship with others , including the husb and , and impaired coping skills appeared to be independent risk factors for the development of symptomatic preterm labor in urbanized women OBJECTIVE Selective serotonin reuptake inhibitor ( SSRI ) use during pregnancy incurs a low absolute risk for major malformations ; however , other adverse outcomes have been reported . Major depression also affects reproductive outcomes . This study examined whether 1 ) minor physical anomalies , 2 ) maternal weight gain and infant birth weight , 3 ) preterm birth , and 4 ) neonatal adaptation are affected by SSRI or depression exposure . METHOD This prospect i ve observational investigation included maternal assessment s at 20 , 30 , and 36 weeks of gestation . Neonatal outcomes were obtained by blinded review of delivery records and infant examinations . Pregnant women ( N=238 ) were categorized into three mutually exclusive exposure groups : 1 ) no SSRI , no depression ( N=131 ) ; 2 ) SSRI exposure ( N=71 ) , either continuous ( N=48 ) or partial ( N=23 ) ; and 3 ) major depressive disorder ( N=36 ) , either continuous ( N=14 ) or partial ( N=22 ) . The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups , demonstrating the expected treatment effect of SSRIs . Main outcomes were minor physical anomalies , maternal weight gain , infant birth weight , pregnancy duration , and neonatal characteristics . RESULTS Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure . Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain . Mean infant birth weights were equivalent . Other neonatal outcomes were similar , except 5-minute Apgar scores . CONCLUSIONS For depressed pregnant women , both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20 % BACKGROUND The impact of prenatal depression on pregnancy outcomes is largely unknown . METHODS We conducted a population -based prospect i ve cohort study among pregnant women of the Kaiser Permanente Medical Care Program to examine the impact of prenatal depression on the risk of preterm delivery . We interviewed pregnant women in their early pregnancy . Women 's depressive symptoms were ascertained using the st and ard Center for Epidemiological Studies Depression Scale ( CESD ) . The presence of significant prenatal depressive symptoms and severe depressive symptoms was determined by CESD scores > or = 16 and > or = 22 , respectively . RESULTS Among the 791 participants who answered CESD questions and delivered a live birth , after controlling for potential confounders using the Cox proportional hazard regression , women with CESD scores > or = 16 had almost twice the risk of preterm delivery compared with women without depressive symptoms : adjusted hazard ratio ( aHR ) = 1.9 , 95 % confidence interval ( CI ) 1.0 - 3.7 . The risk of preterm delivery increased with increasing severity of depression : aHR = 1.6 ( CI 0.7 - 3.6 ) for CESD 16 - 21 and aHR = 2.2 ( CI 1.1 - 4.7 ) for CESD > or = 22 . The risk of preterm delivery associated with prenatal depression appears to be exacerbated by low educational level , a history of fertility problems and the presence of obesity and stressful events . The observed associations were not confounded by the use of antidepressants , although some of the associations did not reach statistical significance . CONCLUSIONS Our findings show that pregnant women with depressive symptoms are at increased risk of preterm delivery and , in addition , provide preliminary evidence that social and reproductive risk factors as well as obesity and stressful events may exacerbate the effect Objective : The high rate of preterm births is an imposing public health issue in the United States . Past research has suggested that prenatal stress , anxiety , and elevated levels of maternal plasma corticotropin-releasing hormone ( CRH ) are associated with preterm delivery in humans and animals . Studies to date have not examined all three variables together ; that is the objective of this paper . Methods : Data from 282 pregnant women were analyzed to investigate the effect of maternal prenatal anxiety and CRH on the length of gestation . It was hypothesized that at both 18 to 20 weeks ( Time 1 ) and 28 to 30 weeks gestation ( Time 2 ) , CRH and maternal prenatal anxiety would be negatively associated with gestational age at delivery . CRH was also expected to mediate the relationship between maternal prenatal anxiety and gestational age at delivery . Results : Findings supported the mediation hypothesis at Time 2 , indicating that women with high CRH levels and high maternal prenatal anxiety at 28 to 30 weeks gestation delivered earlier than women with lower CRH levels and maternal prenatal anxiety . Women who delivered preterm had significantly higher rates of CRH at both 18 to 20 weeks gestation and 28 to 30 weeks gestation ( p < .001 ) compared with women who delivered term . Conclusions : These findings are the first to link both psychosocial and neuroendocrine factors to birth outcomes in a prospect i ve design . ANOVA = analysis of variance ; BIPS = Behavior in Pregnancy Study ; CRH = corticotropin-releasing hormone ; HPA = hypothalamic-pituitary-adrenal axis ; SNS = sympathetic nervous system OBJECTIVE The aim was to test a model of the influence of maternal prenatal psychosocial stress on birth outcomes after controlling for biomedical risk . STUDY DESIGN In a prospect i ve study a sociodemographically homogeneous sample of 90 women was assessed during the third trimester with st and ard , reliable question naires that measured episodic and chronic stress , strain ( response to stress ) , and pregnancy-related anxiety . Birth outcomes included infant birth weight , gestational age at birth , and intrapartum complications . Parity and biomedical ( antepartum ) risk was also coded . Bivariate and multivariate analyses were performed after controlling for the effects of biomedical risk factors . RESULTS Independent of biomedical risk , each unit increase of prenatal life event stress ( from a possible sample range of 14.7 units ) was associated with a 55.03 gm decrease in infant birth weight and with a significant increase in the likelihood of low birth weight ( odds ratio 1.32 ) , and each unit increase of prenatal pregnancy anxiety ( from a possible sample range of 5 units ) was associated with a 3-day decrease in gestational age at birth . CONCLUSION Independent of biomedical risk , maternal prenatal stress factors are significantly associated with infant birth weight and with gestational age at birth Objectives : This study examined associations between reported pregnancy intendedness and several maternal psychosocial factors in relation to preterm birth ( < 37 weeks ' completed gestation ) . Methods : Women were recruited into a prospect i ve cohort study between the 24th and 29th weeks of pregnancy in central North Carolina from 1996 to 2000 . Prior to delivery , participants responded to questions about pregnancy intendedness , life events impacts , depressive symptoms , and coping style . Results : Women who reported not intending their pregnancy had increased odds of reporting low , medium and high levels of perceived stress during pregnancy ( OR = 1.4 [ 95 % CI : 1.1 , 1.9 ] , OR = 2.2 [ 95 % CI : 1.7 , 2.8 ] , and OR = 3.4 [ 95 % CI : 2.6 , 4.5 ] , respectively , relative to very low ) , medium and high levels of depressive symptoms ( OR = 2.2 [ 95 % CI : 1.8 , 2.9 ] and OR = 3.1 [ 95 % CI : 2.4 , 3.9 ] , respectively ) , and medium and high levels of several coping styles . Reporting not intending the pregnancy was not associated with increased risk of preterm birth ( Risk Ratio [ RR ] = 1.0 , 95 % CI : 0.8 , 1.1 ) , but reporting the highest quartile of perceived stress ( RR = 1.6 , 95 % CI : 1.1 , 2.3 ) and the highest tertile of distancing coping style ( compared with lowest quartile ) was associated with preterm birth ( RR = 1.4 , 95 % CI : 1.1 , 1.9 ) . Interactions between pregnancy intendedness and the psychosocial variables perceived stress , depression or coping style did not modify the psychosocial variable 's associations with preterm birth . Conclusions : Pregnancy intendedness remains an important concept in the reproductive health literature integrally tied to indicators of maternal mental health , but not necessarily to pregnancy outcomes OBJECTIVES To identify and evaluate which psychosocial criteria are associated with preterm birth in a midwifery model of risk in pregnancy . DESIGN A quantitative study with a prospect i ve correlational research design . SETTING Women attending three prenatal clinics in East Tennessee . PARTICIPANTS 120 pregnant women between 16 and 28 weeks gestation . The majority of the clinics ' clients were from rural Appalachia . MEASUREMENTS AND FINDINGS Multiple logistic regression statistical analysis revealed that women with symptoms of depression , lower levels of self-esteem , or a negative perception of pregnancy had significantly higher odds of delivering a preterm baby . KEY CONCLUSIONS AND IMPLICATION S FOR PRACTICE These findings suggest the importance of screening for psychosocial risk factors in pregnancy . Interventions to address these psychosocial risks could improve maternal psychosocial health , maintain continuity of midwifery care , and reduce the incidence of preterm birth Background . The influence of psychosocial factors such as stress , anxiety , depression , and self‐esteem on birth weight is controversial . A prospect i ve study was conducted to evaluate the relationship between pregnancy outcomes , psychosocial profile , and maternal health practice s. Methods . 3,149 low‐income , predominantly African‐American pregnant women participated in this study . A 28‐item psychosocial scale measured the constructs of negative and positive affect , self esteem , mastery , worry , and stress . Maternal health practice s were assessed with 11 questions dealing with diet , exercise , and the use of preventive medical and dental services . Results . A low score on either scale indicated “ poor ” psychosocial or health practice s status . Low birth weight , preterm delivery , and intrauterine growth retardation occurred in 10.9 , 10.1 and 7.3 % of the pregnant women respectively . In women with low psychosocial scores , the risk of both low birth weight and preterm delivery was 40 % higher and the mean birth weight of infants was 51 g ( p=0.02 ) lower as compared to women with high scores . Negative affect ( a measure of depression ) was the only factor significantly associated with both infant birth weight ( β= − 71.2 , p=0.001 ) and low birth weight ( AOR = 1.4 , 95 % CI = 1.1–1.7 ) . When data were stratified by body mass index , the adverse effect of negative affect scores on birth weight and low birth weight was present only in thin women . Health practice scores were not associated with any of the pregnancy outcomes . Conclusion . Thin women with a poor psychosocial profile and who are depressed during pregnancy are at increased risk of giving birth to low birth weight and preterm infants Objective . To estimate the association between common mental disorders ( CMD ) during pregnancy and risk of low birth weight ( LBW ) or preterm birth ( PTB ) . Methods . A prospect i ve cohort study was conducted with 831 pregnant women from antenatal clinics in primary healthcare in São Paulo , Brazil . The clinical interview schedule-revised and demographic question naires were administered between the 20th and 30th weeks of gestation . Information on infant weight and gestational age at birth were obtained from hospital records . Univariate analyses were used to examine the association between the main exposure and main outcomes . Statistical associations were examined with χ2 tests . Adjusted odds ratios ( OR ) and 95 % confidence intervals ( CI ) for the main outcomes were obtained using a multivariable logistic regression model . Results . The prevalence of CMD during gestation was 33.6 ( 95 % CI : 30.4–36.9 ) . The follow-up rate was 99.5 % . Sixty three ( 7.6 % ) newborns were classified as LBW and 56 ( 6.9 % ) were classified as PTB . CMD during pregnancy was not associated with risk of PTB ( adjusted OR:1.03 , 95 % CI : 0.57–1.88 ) or LBW ( adjusted OR:1.09 , 95 % CI : 0.62–1.91 ) . Conclusions . CMD prevalence is high among low-income and low-risk pregnant women attended by public health services in a middle-income country , but not confer an increased risk for adverse obstetric outcome OBJECTIVE The authors evaluated the effects of prenatal antidepressant exposure and maternal depression on infant gestational age at birth and risk of preterm birth . METHOD Ninety women were followed in a prospect i ve , naturalistic design through pregnancy with monthly assessment s of symptoms of depression and anxiety using the Structured Clinical Interview for DSM-IV mood module for depression , the Hamilton Depression Rating Scale , the Beck Depression Inventory , and the Perceived Stress Scale . Participants included 49 women with major depressive disorder who were treated with antidepressants during pregnancy ( group 1 ) , 22 women with major depressive disorder who were either not treated with antidepressants or had limited exposure to them during pregnancy ( group 2 ) , and 19 healthy comparison subjects ( group 3 ) . The primary outcome variables were the infants ' gestational age at birth , birth weight , 1- and 5-minute Apgar scores , and admission to the special care nursery . RESULTS Groups 1 , 2 , and 3 differed significantly in gestational age at birth ( 38.5 weeks , 39.4 weeks , 39.7 weeks , respectively ) , rates of preterm birth ( 14.3 % , 0 % , 5.3 % , respectively ) , and rates of admission to the special care nursery ( 21 % , 9 % , 0 % , respectively ) . Birth weight and Apgar scores did not differ significantly between groups . Mild to moderate depression during pregnancy did not affect outcome measures . CONCLUSIONS Prenatal antidepressant use was associated with lower gestational age at birth and an increased risk of preterm birth . Presence of depressive symptoms was not associated with this risk . These results suggest that medication status , rather than depression , is a predictor of gestational age at birth This study investigated the prevalence of preterm birth and low-birth-weight in Macao . It also evaluated the effects of maternal perceived stress and health-related quality of life on these 2 birth outcomes . A quantitative study using a prospect i ve longitudinal design was undertaken in an antenatal clinic in Macao . A community-based sample ( N = 581 ) of pregnant women in their second trimester was recruited ; birth outcome data were collected from medical records . Perceived stress was measured using the Perceived Stress Scale , whereas health-related quality of life was measured using the st and ard SF-12 Health Survey . The prevalence rates of preterm birth and low-birth-weight were found to be 6.4 % and 7.1 % , respectively . Two multiple logistic regression analyses revealed that participants with past adverse obstetric complications and higher perceived stress levels were more likely to have premature infants . Also , those participants with higher perceived stress levels and poorer health-related quality of life in the physical health domain were more likely to have low-birth-weight infants . Preliminary information was provided on risk factors associated with adverse birth outcomes ; this could help nurses to design appropriate risk-specific interventions for preventing preterm birth and low-birth-weight Nulliparous women with singleton gestation were assessed prospect ively for anxiety levels with the State-Trait Anxiety Inventory , which measured state ( situational and transitional ) and trait ( dispositional and stable ) anxiety , with high scores indicating high anxiety . Bivariate and multivariate methods were used for data analysis . Anxiety assessment s ( n = 239 ) were obtained in 88 women at different stages of gestation . Mean anxiety scores were lowest at 22 to 26 weeks . A woman 's successive scores were highly correlated . The trait anxiety ( A-T ) scores were higher for married women . A positive correlation was present between anxiety scores and gestational age at delivery . Low A-T scores correlated with low birthweight , preterm delivery , and chorioamnionitis . High state anxiety ( A-S ) levels correlated with the presence of meconium in the amniotic fluid and neonatal congenital abnormalities . Post date delivery also was associated with higher although statistically insignificant anxiety scores . Women who presented to the labor and delivery room for various complaints had higher A-S and A-T levels . Maternal anxiety level was associated with adverse perinatal outcome ; specifically , prematurity and low birthweight correlated with low A-T levels Background : Major depressive disorder and the use of serotonin reuptake inhibitors ( SRIs ) in pregnancy have been associated with preterm birth . Studies that have attempted to separate effects of illness from treatment have been inconclusive . We sought to explore the separate effects of SRI use and major depressive episodes in pregnancy on risk of preterm birth . Methods : We conducted a prospect i ve cohort study of 2793 pregnant women , over sample d for a recent episode of major depression or use of an SRI . We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth ( < 37 weeks ' gestation ) . We used ordered logistic regression to model early ( < 34 weeks ' gestation ) or late ( 34–36 weeks ) preterm birth , and we used nominal logistic regression to model preterm birth antecedents ( spontaneous preterm labor/preterm premature rupture of membranes/preterm for medical indications/term ) . Results : Use of an SRI , both with ( odds ratio = 2.1 [ 95 % confidence interval = 1.0–4.6 ] ) and without ( 1.6 [ 1.0–2.5 ] ) a major depressive episode , was associated with preterm birth . A major depressive episode without SRI use ( 1.2 [ 0.68–2.1 ] ) had no clear effect on preterm birth risk . None of these exposures was associated with early preterm birth . Use of SRIs in pregnancy was associated with increases in spontaneous but not medically indicated preterm birth . Conclusions : SRI use increased risk of preterm birth . Although the effect of a major depressive episode alone was unclear , symptomatic women undergoing antidepressant treatment had elevated risk OBJECTIVE To investigate the effects of anxiety and depression during pregnancy on obstetric complications using the data collected from the St George 's Birthweight Study . DESIGN Prospect i ve population study . SETTING District general hospital in inner London . SUBJECTS A consecutive series of 1860 white women booking for delivery were approached . Of these , 136 refused and 209 failed to complete the study for other reasons , leaving a sample of 1515 . MAIN OUTCOME MEASURE Data were obtained by research interviewers at booking , 17 , 28 , and 36 weeks gestation and from the structured antenatal and obstetric record . The predictor variables were the anxiety and depression scores measured using the General Health Question naire . The outcome variables were five obstetric complications : preterm delivery ; nonspontaneous onset of labour ; major analgesia in the first and second stages of labour ; and nonspontaneous vaginal deliveries . The possible confounding effects of 35 socio-economic , psychological and personal variables were investigated using logistic regression . RESULTS The factors that had the strongest relation with the outcomes were parity and maternal age . Depression during pregnancy was unrelated to the obstetric complications . Anxiety was weakly related to analgesia/anaesthesia in the second stage of labour ( P = 0.04 ) . However , anxiety accounted for only 0.1 % of the variance in use of major analgesia/anaesthesia . The most effective model , that for analgesia/anaesthesia in the first stage of labour , accounted for only 7.3 % of the variance . CONCLUSIONS In the general population of pregnant women , anxiety and depression during pregnancy , while undesirable in themselves , are of little importance in the evolution of obstetric complications The purpose of this study was to examine the relation between maternal depressive symptoms and spontaneous preterm birth . From 1991 to 1993 , pregnant , African-American women were prospect ively enrolled at four hospital-based clinics in Baltimore , Maryl and , that serve low-income areas of the city . The Center for Epidemiologic Studies Depression ( CES-D ) Scale was used to assess depressive symptoms . Multiple logistic regression analysis estimated the independent contribution of maternal depressive symptoms to spontaneous preterm birth , controlling for behavioral , clinical , and demographic variables . Among the 1,399 women in the sample , 117 ( 8.4 % ) had a spontaneous preterm delivery . Spontaneous preterm birth occurred among 12.7 % of those with a CES-D score in the upper 10th percentile and among 8.0 % of those with a lower score ( relative risk = 1.59 ) . The adjusted odds ratio for an elevated CES-D score was 1.96 ( 95 % confidence interval : 1.04 , 3.72 ) ; hence , maternal depressive symptoms in this sample of African-American women were independently associated with spontaneous preterm birth . Effective treatment of depression in pregnant women could ultimately result in a reduction of spontaneous preterm births This study examined a comprehensive array of psychosocial factors , including life events , social support , depression , pregnancy-related anxiety , perceived discrimination , and neighborhood safety in relation to preterm birth ( < 37 weeks ) in a prospect i ve cohort study of 1,962 pregnant women in central North Carolina between 1996 and 2000 , in which 12 % delivered preterm . There was an increased risk of preterm birth among women with high counts of pregnancy-related anxiety ( risk ratio ( RR ) = 2.1 , 95 % confidence interval ( CI ) : 1.5 , 3.0 ) , with life events to which the respondent assigned a negative impact weight ( RR = 1.8 , 95 % CI : 1.2 , 2.7 ) , and with a perception of racial discrimination ( RR = 1.4 , 95 % CI : 1.0 , 2.0 ) . Different levels of social support or depression were not associated with preterm birth . Preterm birth initiated by labor or ruptured membranes was associated with pregnancy-related anxiety among women assigning a high level of negative impact weights ( RR = 3.0 , 95 % CI : 1.7 , 5.3 ) . The association between high levels of pregnancy-related anxiety and preterm birth was reduced when restricted to women without medical comorbidities , but the association was not eliminated . The prospect i ve collection of multiple psychosocial measures on a large population of women indicates that a subset of these factors is associated with preterm birth PURPOSE This study examined the associations among maternal depression , measured in several ways , psychiatric medication use in pregnancy , and preterm delivery ( PTD ) . METHODS Data were collected from 3,019 women enrolled in the Pregnancy Outcomes and Community Health Study ( 1998 - 2004 ) , a prospect i ve study of pregnant women in five Michigan communities . Information on depressive symptoms , history of depression , and psychiatric medication use was ascertained through interviews at mid-pregnancy . These variables and other relevant covariates were incorporated into regression models with a binary outcome , that is , term ( > or = 37 weeks ' gestation ) as referent and PTD ( < 37 weeks ' gestation ) . A second set of models used a multicategory outcome , namely , term as the referent and PTD further subdivided by gestational weeks and clinical circumstances . MAIN FINDINGS The odds of overall PTD was increased among women who used psychiatric medication during pregnancy and had either elevated levels of depressive symptoms at mid-pregnancy ( adjusted odds ratio [ AOR ] , 2.0 ; 95 % confidence interval [ CI ] , 1.1 - 3.6 ) or a history of depression before pregnancy ( AOR , 1.6 ; 95 % CI , 1.1 - 2.5 ) . The combination of psychiatric medication use in pregnancy and depression , before pregnancy , or within pregnancy was most strongly linked to a medically indicated delivery before 35 weeks ' gestation ( AOR , 2.9 and 3.6 , respectively ) . CONCLUSIONS There are at least two plausible explanations for these findings . First , psychiatric medication use in pregnancy may pose an excess risk of PTD . Second , medication use may be an indicator of depressive symptom severity , which is a direct or indirect ( i.e. , alters behavior ) contributing factor to PTD |
489 | 32,061,264 | The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine | Migraine is one of the most common neurological disorders that leads to disabilities .
However , the conventional drug therapy for migraine might be unsatisfactory at times .
Therefore , this meta- analysis aim ed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody ( CGRP mAb ) for the preventive treatment of episodic migraine , and provide high- quality clinical evidence for migraine therapy . | BACKGROUND Calcitonin gene-related peptide ( CGRP ) is a vali date d target for the treatment of episodic migraine . Here we assess the safety , tolerability , and efficacy of TEV-48125 , a monoclonal anti-CGRP antibody , in the preventive treatment of high-frequency episodic migraine . METHODS In this multicentre , r and omised , double-blind , placebo-controlled , phase 2b study , we enrolled men and women ( aged 18 - 65 years ) from 62 sites in the USA who had migraine headaches 8 - 14 days per month . Using a r and omisation list generated by a central computerised system and an interactive web response system , we r and omly assigned patients ( 1:1:1 ; stratified by sex and use of concomitant preventive drugs ) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125 , 675 mg TEV-48125 , or placebo . Investigators , patients , and the funder were blinded to treatment allocation . Patients reported headache information daily using an electronic diary . Primary endpoints were change from baseline in migraine days during the third treatment cycle ( weeks 9 - 12 ) and safety and tolerability . The secondary endpoint was change relative to baseline in headache-days during weeks 9 - 12 . Efficacy endpoints were analysed for the intention-to-treat population . Safety and tolerability were analysed using descriptive statistics . This trial is registered at Clinical Trials.gov , number NCT02025556 . FINDINGS Between Jan 8 , 2014 , and Oct 15 , 2014 , we enrolled 297 participants : 104 were r and omly assigned to receive placebo , 95 to receive 225 mg TEV-48125 , and 96 to receive 675 mg TEV-48125 . The least square mean ( LSM ) change in number of migraine-days from baseline to weeks 9 - 12 was -3.46 days ( SD 5.40 ) in the placebo group , -6.27 days ( 5.38 ) in the 225 mg dose group , and -6.09 days ( 5.22 ) in the 675 mg dose group . The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days ( 95 % CI -4.07 to -1.55 ; p<0.0001 ) , whereas the difference between the placebo and 675 mg dose group was -2.64 days ( -3.90 to -1.38 ; p<0.0001 ) . LSM differences in the reduction of headache-days were -2.63 days ( -3.91 to -1.34 ; p<0.0001 ) between the placebo group and 225 mg dose group and -2.58 days ( -3.87 to 1.30 ; p < 0.0001 ) between the placebo group and the 675 mg dose group . Adverse events occurred in 58 ( 56 % ) patients in the placebo group , 44 ( 46 % ) patients in the 225 mg dose group , and 57 ( 59 % ) patients in the 675 mg dose group ; moderate or severe adverse events were reported for 29 ( 27 % ) patients , 24 ( 25 % ) patients , and 26 ( 27 % ) patients , respectively . INTERPRETATION TEV-48125 , at doses of 225 mg and 675 mg given once every 28 days for 12 weeks , was safe , well tolerated , and effective as a preventive treatment of high-frequency episodic migraine , thus supporting advancement of the clinical development programme to phase 3 clinical trials . FUNDING Teva Pharmaceuticals BACKGROUND Benefits of calcitonin-gene related peptide ( CGRP ) inhibition have not been established in chronic migraine . Here we assess the safety , tolerability , and efficacy of two doses of TEV-48125 , a monoclonal anti-CGRP antibody , in the preventive treatment of chronic migraine . METHODS In this multicentre , r and omised , double-blind , double-dummy , placebo-controlled , parallel-group phase 2b study , we enrolled men and women ( aged 18 - 65 years ) from 62 sites in the USA who had chronic migraine . Using a r and omisation list generated by a central computerised system and an interactive web response system , we r and omly assigned patients ( 1:1:1 , stratified by sex and use of concomitant preventive drugs ) to three 28-day treatment cycles of subcutaneous TEV-48125 675/225 mg ( 675 mg in the first treatment cycle and 225 mg in the second and third treatment cycles ) , TEV-48125 900 mg ( 900 mg in all three treatment cycles ) , or placebo . Investigators , patients , and the funder were blinded to treatment allocation . Daily headache information was captured using an electronic diary . Primary endpoints were change from baseline in the number of headache-hours during the third treatment cycle ( weeks 9 - 12 ) and safety and tolerability during the study . Secondary endpoint was change in the number of moderate or severe headache-days in weeks 9 - 12 relative to baseline . Efficacy endpoints were analysed for the intention-to-treat population . Safety and tolerability were analysed using descriptive statistics . This trial is registered with Clinical Trials.gov , number , NCT02021773 . FINDINGS Between Jan 8 , 2014 , and Aug 27 , 2014 , we enrolled 264 participants : 89 were r and omly assigned to receive placebo , 88 to receive 675/225 mg TEV-48125 , and 87 to receive 900 mg TEV-48125 . The mean change from baseline in number of headache-hours during weeks 9 - 12 was -59.84 h ( SD 80.38 ) in the 675/225 mg group and -67.51 h ( 79.37 ) in the 900 mg group , compared with -37.10 h ( 79.44 ) in the placebo group . The least square mean difference in the reduction of headache-hours between the placebo and 675/225 mg dose groups was -22.74 h ( 95 % CI -44.28 to -1.21 ; p=0.0386 ) , whereas the difference between placebo and 900 mg dose groups was -30.41 h ( -51.88 to -8.95 ; p=0.0057 ) . Adverse events were reported by 36 ( 40 % ) patients in the placebo group , 47 ( 53 % ) patients in the 675/225 mg dose group , and 41 ( 47 % ) patients in the 900 mg dose group , whereas treatment-related adverse events were recorded in 15 ( 17 % ) patients , 25 ( 29 % ) patients , and 28 ( 32 % ) patients , respectively . The most common adverse events were mild injection-site pain and pruritus . Four ( 1 % ) patients had serious non-treatment-related adverse events ( one patient in the placebo group , one patient in the 675/225 mg group , and two patients in the 900 mg group ) ; no treatment-related adverse events were serious and there were no relevant changes in blood pressure or other vital signs . INTERPRETATION TEV-48125 given by subcutaneous injection every 28 days seems to be tolerable and effective , thus supporting the further development of TEV-48125 for the preventive treatment of chronic migraine in a phase 3 trial . FUNDING Teva Pharmaceuticals Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology . Erenumab , a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor , is being evaluated for migraine prevention . Methods In this r and omized , double-blind , placebo-controlled , phase 3 study , 577 adults with episodic migraine were r and omized to placebo or 70 mg erenumab ; 570 patients were included in efficacy analyses . Primary endpoint was change in monthly migraine days . Secondary endpoints were ≥50 % reduction in monthly migraine days , change in acute migraine-specific medication treatment days , and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary . All endpoints assessed change from baseline at month 3 . Results Patients receiving erenumab experienced −2.9 days change in monthly migraine days , compared with −1.8 days for placebo , least-squares mean ( 95 % CI ) treatment difference of −1.0 ( −1.6 , −0.5 ) ( p < 0.001 ) . A ≥ 50 % reduction in monthly migraine days was achieved by 39.7 % ( erenumab ) and 29.5 % ( placebo ) of patients ( OR:1.59 ( 95 % CI : 1.12 , 2.27 ) ( p = 0.010 ) . Migraine-specific medication treatment days were reduced by −1.2 ( erenumab ) and −0.6 ( placebo ) days , a treatment difference of −0.6 ( −1.0 , −0.2 ) ( p = 0.002 ) . The ≥5-point reduction rates in Migraine Physical Function Impact Diary – Physical Impairment were 33.0 % and 27.1 % ( OR:1.33 ( 0.92 , 1.90 ) ( p = 0.13 ) and in Migraine Physical Function Impact Diary – Everyday Activities were 40.4 % and 35.8 % ( OR:1.22 ( 0.87 , 1.71 ) ( p = 0.26 ) . Safety and adverse event profiles of erenumab were similar to placebo . Most frequent adverse events were upper respiratory tract infection , injection site pain , and nasopharyngitis . Conclusions As a preventive treatment of episodic migraine , erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use . ( Funded by Amgen ) . Trial registration Clinical Trials.gov , NCT02483585 Importance Galcanezumab ( LY2951742 ) , a monoclonal antibody against calcitonin gene-related peptide ( CGRP ) , is one of a novel class of new medicines for migraine prevention . Objective To assess whether at least 1 dose of galcanezumab was superior to placebo for episodic migraine prevention . Design , Setting , and Participants A r and omized clinical trial was conducted in the United States ( July 7 , 2014 , to August 19 , 2015 ) in clinics of 37 licensed physicians with a specialty including , but not limited to , psychiatry , neurology , internal medicine , and primary care . Subcutaneous injections of galcanezumab , 5 , 50 , 120 , or 300 mg , or placebo were given monthly during the 3-month treatment period . A total of 936 patients were assessed ; 526 did not meet study entry or baseline criteria and 410 patients were r and omly assigned to receive placebo or galcanezumab . Analyses were conducted on an intent-to-treat population , which included all patients who were r and omized and received at least 1 dose of study drug . Interventions Short-term migraine treatments were allowed as needed except for opioids or barbiturates . Main Outcomes and Measures To determine if at least 1 of the 4 doses of galcanezumab tested was superior to placebo for migraine prevention measured by the mean change from baseline in the number of migraine headache days 9 weeks to 12 weeks after r and omization . Results Of the 936 patients assessed , 410 met entry criteria ( aged 18 - 65 years with 4 - 14 migraine headache days per month and migraine onset prior to age 50 years ) and were r and omized to receive placebo or galcanezumab . For the primary end point , galcanezumab , 120 mg , significantly reduced migraine headache days compared with placebo ( 99.6 % posterior probability −4.8 days ; 90 % BCI , −5.4 to −4.2 days vs 95 % superiority threshold [ Bayesian analysis ] −3.7 days ; 90 % BCI , −4.1 to −3.2 days ) . Adverse events reported by 5 % or more of patients in at least 1 galcanezumab dose group and more frequently than placebo included injection-site pain , upper respiratory tract infection , nasopharyngitis , dysmenorrhea , and nausea . Conclusions and Relevance Monthly subcutaneous injections of galcanezumab , both 120 mg and 300 mg , demonstrated efficacy ( repeated- measures analysis ) for the preventive treatment of migraine and support further development in larger phase 3 studies . All dosages were safe and well tolerated for the preventive treatment of episodic migraine . Trial Registration clinical trials.gov Identifier : Monoclonal antibodies ( mAbs ) targeting calcitonin gene‐related peptide ( CGRP ) signaling are being explored as prophylactic treatments for migraine . Erenumab ( AMG 334 ) is the first potent , selective , and competitive human mAb antagonist of the CGRP receptor . We report the data from two phase I studies assessing the safety , pharmacokinetics ( PK ) , and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine . The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies . Single doses of erenumab result ed in > 75 % inhibition of capsaicin‐induced dermal blood flow , with no apparent dose‐dependency for erenumab ≥21 mg . Erenumab was generally well tolerated , with an acceptable safety profile , supporting further clinical development of erenumab for migraine prevention Objectives The primary and secondary objectives of this phase 1 study were to evaluate the pharmacokinetic profile , safety , and immunogenicity of fremanezumab subcutaneous ( sc ) doses tested in phase 2 and 3 trials ( 225 mg , 675 mg and 900 mg ) following single administration in Japanese ( n = 32 ) and Caucasian ( n = 32 ) healthy subjects . Methods Japanese and matched Caucasian healthy subjects were enrolled into one of four cohorts and were r and omly assigned to one of four treatments : 225 , 675 , or 900 mg fremanezumab , or placebo . Pharmacokinetic and immunogenicity sampling , and safety and tolerability assessment s occurred at one inpatient visit and 12 ambulatory visits during the 36-week study . Results Pharmacokinetic analyses included those r and omized to fremanezumab ( n = 24 for each ethnic group ) and safety analyses included all subjects enrolled in the study ( n = 32 for each ethnic group ) . Fremanezumab concentration-time profiles and pharmacokinetic parameters per dose were similar for Japanese and Caucasians at all dose levels . Geometric mean ratios ( GMRs ) for Cmax for Japanese to Caucasian subjects were 0.91 , 1.04 and 1.14 for the 225 mg , 675 mg and 900 mg fremanezumab doses . GMRs for AUC0-inf were 0.96 , 1.09 , and 0.98 , respectively . Median Tmax ( range 5–11 days ) and mean half-lives ( range 31–39 days ) were similar across doses for both ethnicities . Most frequently occurring adverse events were injection site reactions , abdominal pain , headache , upper respiratory tract infection , constipation and nasopharyngitis . There was no development of anti-drug-antibodies and no clinical ly meaningful changes in laboratory findings . Conclusion The results of the pharmacokinetic exposure parameters and safety measures were similar for Japanese and Caucasians and support the once monthly and once quarterly sc injections of fremanezumab BACKGROUND Migraine remains poorly treated , with few effective preventive drugs available . We assessed the safety and efficacy of LY2951742 , a fully humanised monoclonal antibody to calcitonin gene-related peptide , for migraine prevention . METHODS We did a r and omised , double-blind , placebo-controlled , phase 2 proof-of-concept study at 35 centres in the USA . Patients aged 18 - 65 years with four to 14 migraine headache days per month were r and omly assigned ( 1:1 ) to LY2951742 or placebo by a computerised r and omisation scheme . LY2951742 ( 150 mg ) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks . The primary endpoint was the mean change in number of migraine headache days per 28-day period assessed at 9 - 12 weeks . Safety was assessed over 24 weeks , including the 12-week treatment period and the subsequent 12 weeks after study drug administration . Patients and treating investigators were masked to treatment allocation . Analyses were by intention to treat . A mixed-effects model of repeated measures was used , including patient baseline value , treatment , visit , and treatment-by-visit interaction as fixed effects , and patients as r and om effects . Safety measures were analysed according to the treatment received . This study has been completed and is registered with Clinical Trials.gov , NCT01625988 . FINDINGS Between July 31 , 2012 , and Sept 18 , 2013 , 218 patients were r and omly assigned to LY2951742 ( n=108 , but one patient withdrew before treatment ) or placebo ( n=110 ) . The mean change from baseline to week 12 in the number of migraine headache days was -4·2 ( SD 3·1 ; 62·5 % decrease ) in the LY2951742 group compared with -3·0 ( SD 3·0 ; 42·3 % decrease ) in the placebo group ( least-squares mean difference -1·2 , 90 % CI -1·9 to -0·6 ; p=0·0030 ) . Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain , erythema , or both ( 21 [ 20 % ] of 107 vs seven [ 6 % ] of 110 ) , upper respiratory tract infections ( 18 [ 17 % ] vs ten [ 9 % ] ) , and abdominal pain ( six [ 6 % ] vs three [ 3 % ] ) . There were two serious adverse events reported in the treatment arm and four in the placebo arm , none of which were deemed to be related to the study drug . INTERPRETATION These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine . Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine . FUNDING Arteaus Therapeutics BACKGROUND The calcitonin gene-related peptide ( CGRP ) pathway is a promising target for preventive therapies in patients with migraine . We assessed the safety and efficacy of AMG 334 , a fully human monoclonal antibody against the CGRP receptor , for migraine prevention . METHODS In this multicentre , r and omised , double-blind , placebo-controlled , phase 2 trial , patients aged 18 - 60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe , and r and omly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo , AMG 334 7 mg , AMG 334 21 mg , or AMG 334 70 mg using a sponsor-generated r and omisation sequence central ly executed by an interactive voice response or interactive web response system . Study site personnel , patients , and the sponsor study personnel were masked to the treatment assignment . The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase . The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures . Safety endpoints were adverse events , clinical laboratory values , vital signs , and anti-AMG 334 antibodies . The study is registered with Clinical Trials.gov , number NCT01952574 . An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334 . FINDINGS From Aug 6 , 2013 , to June 30 , 2014 , 483 patients were r and omly assigned to placebo ( n=160 ) , AMG 334 7 mg ( n=108 ) , AMG 334 21 mg ( n=108 ) , or AMG 334 70 mg ( n=107 ) . The mean change in monthly migraine days at week 12 was -3·4 ( SE 0·4 ) days with AMG 334 70 mg versus -2·3 ( 0·3 ) days with placebo ( difference -1·1 days [ 95 % CI -2·1 to -0·2 ] , p=0·021 ) . The mean reductions in monthly migraine days with the 7 mg ( -2·2 [ SE 0·4 ] ) and the 21 mg ( -2·4 [ 0·4 ] ) doses were not significantly different from that with placebo . Adverse events were recorded in 82 ( 54 % ) patients who received placebo , 54 ( 50 % ) patients in the AMG 334 7 mg group , 54 ( 51 % ) patients in the AMG 334 21 mg group , and 57 ( 54 % ) patients in the AMG 334 70 mg group . The most frequently reported adverse events were nasopharyngitis , fatigue , and headache . Serious adverse events were reported for one patient in the AMG 334 7 mg group ( ruptured ovarian cyst ) and one patient in the AMG 334 70 mg group ( migraine and vertigo ) ; these events were judged to be unrelated to AMG 334 treatment . Nine ( 3 % ) of 317 patients had neutralising antibodies . No apparent association was recorded between patients with positive anti-AMG 334 antibodies and adverse events . No clinical ly significant vital signs , laboratory , or electrocardiogram findings were recorded . INTERPRETATION These results suggest that AMG 334 70 mg might be a potential therapy for migraine prevention in patients with episodic migraine and support further investigation of AMG 334 in larger phase 3 trials . FUNDING Amgen Importance Migraine is a disabling neurological disease characterized by severe headache attacks . Treatment options reduce migraine frequency for many patients , but adverse effects lead to discontinuation in many patients . Objective To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura . Design , Setting , and Participants The EVOLVE-1 ( Evaluation of LY2951742 in the Prevention of Episodic Migraine 1 ) trial was a double-blind , r and omized , placebo-controlled ( January 11 , 2016 , to March 22 , 2017 ) trial comparing galcanezumab ( 120 mg and 240 mg ) vs placebo . Patients received treatments once monthly for 6 months ( subcutaneous injection via prefilled syringe ) and were followed up for 5 months after their last injection . It was a multicenter , clinic-based study involving 90 sites in North America . Participants in the study were adults ( aged 18 to 65 years ) with at least a 1-year history of migraine , 4 to 14 migraine headache days per month and a mean of at least 2 migraine attacks per month within the past 3 months , and were diagnosed prior to age 50 years . During the study , no other preventive medications were allowed . A total of 1671 patients were assessed ; 809 did not meet study entry or baseline criteria , and 858 were included in the intent-to-treat population . Interventions Patients were r and omized ( 2:1:1 ) to monthly placebo , galcanezumab , 120 mg , and galcanezumab , 240 mg . Main Outcomes and Measures The primary outcome was overall mean change from baseline in the number of monthly migraine headache days during the treatment period . Secondary measures included at least 50 % , at least 75 % , and 100 % reduction in monthly migraine headache days , migraine headache days with acute medication use , and scores from the Migraine-Specific Quality of Life question naire , Patient Global Impression of Severity , and Migraine Disability Assessment . Treatment-emergent adverse events and serious adverse events were reported . Results Of the 1671 patients assessed , 858 ( mean age , 40.7 years ; 718 women [ 83.7 % ] ) met study entry criteria and received at least 1 dose of investigational product . The primary objective was met for both galcanezumab doses ; treatment with galcanezumab significantly reduced monthly migraine headache days ( both P < .001 ) by 4.7 days ( 120 mg ) and 4.6 days ( 240 mg ) compared with placebo ( 2.8 days ) . All key secondary objectives were also significant after multiplicity adjustment . There were no meaningful differences between 120-mg and 240-mg doses of galcanezumab on measures of efficacy . Completion rate during treatment was high ( 81.9 % ; n = 718 ) , and the incidence of discontinuation owing to adverse events was less than 5 % across all treatment groups . Conclusions and Relevance Galcanezumab 120-mg and 240-mg monthly injections provided clinical benefits and improved functioning . The incidence rate of adverse events was low , demonstrating the favorable tolerability profile of galcanezumab . Trial Registration Clinical Trials.gov Identifier : Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide , used for migraine prevention . Methods A global , double-blind , 6-month study of patients with episodic migraine was undertaken with 915 intent-to-treat patients r and omized to monthly galcanezumab 120 mg ( n = 231 ) or 240 mg ( n = 223 ) or placebo ( n = 461 ) subcutaneous injections . Primary endpoint was overall mean change from baseline in monthly migraine headache days . Key secondary endpoints were ≥50 % , ≥ 75 % , and 100 % response rates ; monthly migraine headache days with acute migraine medication use ; Patient Global Impression of Severity rating ; the Role Function-Restrictive score of the Migraine-Specific Quality of Life Question naire . Results Mean monthly migraine headache days were reduced by 4.3 and 4.2 days by galcanezumab 120 and 240 mg , respectively , and 2.3 days by placebo . The group differences ( 95 % CIs ) versus placebo were 2.0 ( −2.6 , −1.5 ) and 1.9 ( −2.4 , −1.4 ) , respectively . Both doses were superior to placebo for all key secondary endpoints . Injection site pain was the most common treatment-emergent adverse event , reported at similar rates in all treatment groups . Both galcanezumab doses had significantly more injection site reactions and injection site pruritus , and the 240 mg group had significantly more injection site erythema versus placebo . Conclusions Galcanezumab 120 or 240 mg given once monthly was efficacious , safe , and well tolerated . Study identification EVOLVE-2 ; NCT02614196 ; https:// clinical trials.gov/ct2/show/NCT02614196 . Trial Registration NCT02614196 Importance Fremanezumab , a fully humanized monoclonal antibody that targets calcitonin gene-related peptide , may be effective for treating episodic migraine . Objective To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose . Design and Setting R and omized , double-blind , placebo-controlled , parallel-group trial conducted at 123 sites in 9 countries from March 23 , 2016 ( first patient r and omized ) , to April 10 , 2017 , consisting of a screening visit , 28-day pretreatment period , 12-week treatment period , and final evaluation at week 12 . Participants Study participants were aged 18 to 70 years with episodic migraine ( 6 - 14 headache days , with at least 4 migraine days , during 28-day pretreatment period ) . Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded . Interventions Patients were r and omized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab ( n = 290 ; 225 mg at baseline , week 4 , and week 8) ; a single higher dose of fremanezumab , as intended to support a quarterly dose regimen ( n = 291 ; 675 mg of fremanezumab at baseline ; placebo at weeks 4 and 8) ; or placebo ( n = 294 ; at baseline , week 4 , and week 8) . Main Outcomes and Measures The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose . Results Among 875 patients who were r and omized ( mean age , 41.8 [ SD , 12.1 ] years ; 742 women [ 85 % ] ) , 791 ( 90.4 % ) completed the trial . From baseline to 12 weeks , mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group , from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group , and from 9.1 days to 6.5 days in the placebo group . This result ed in a difference with monthly dosing vs placebo of –1.5 days ( 95 % CI , –2.01 to –0.93 days ; P < .001 ) and with single higher dosing vs placebo of –1.3 days ( 95 % CI , –1.79 to –0.72 days ; P < .001 ) . The most common adverse events that led to discontinuation were injection site erythema ( n = 3 ) , injection site in duration ( n = 2 ) , diarrhea ( n = 2 ) , anxiety ( n = 2 ) , and depression ( n = 2 ) . Conclusions and Relevance Among patients with episodic migraine in whom multiple medication classes had not previously failed , subcutaneous fremanezumab , compared with placebo , result ed in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period . Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy . Trial Registration clinical trials.gov Identifier : BACKGROUND A substantial proportion of patients with migraine does not respond to , or can not tolerate , oral preventive treatments . Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine . We assessed its efficacy and tolerability in patients with episodic migraine in whom previous treatment with two-to-four migraine preventives had been unsuccessful . METHODS LIBERTY was a 12-week , double-blind , placebo-controlled r and omised study at 59 sites in 16 countries . Eligible patients were aged 18 - 65 years and had a history of episodic migraine with or without aura for at least 12 months , had migraine for an average of 4 - 14 days per month during the 3 months before screening , and had been treated unsuccessfully ( in terms of either efficacy or tolerability , or both ) with between two and four preventive treatments . Eligible participants were r and omly assigned ( 1:1 ) to receive either erenumab 140 mg ( via two 70 mg injections ) or placebo every 4 weeks subcutaneously for 12 weeks . R and omisation was by interactive response technology and was stratified by monthly frequency of migraine headache ( 4 - 7 vs 8 - 14 migraine days per month ) during the baseline phase . Cenduit generated the r and omisation list and assigned participants to groups . Participants , investigators , people doing various assessment s , and the study sponsor were masked to treatment assignment . The primary endpoint was the proportion of patients achieving a 50 % or greater reduction in the mean number of monthly migraine days during weeks 9 - 12 . Efficacy was measured in the full analysis set , which included all r and omly assigned patients who started their assigned treatment and completed at least one post-baseline monthly migraine day measurement . Safety and tolerability were assessed by recording adverse events and by physical examination , assessment of vital signs , clinical laboratory assessment s , and electrocardiography . Safety was assessed in all r and omly assigned patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT03096834 . The trial is closed to new participants , but the open-label extension phase is ongoing . FINDINGS Between March 20 , 2017 , and Oct 27 , 2017 , 246 participants were r and omly assigned , 121 to the erenumab group and 125 to the placebo group . 95 of 246 ( 39 % ) participants had previously unsuccessfully tried two preventive drugs , 93 ( 38 % ) had tried three , and 56 ( 23 % ) had tried four . At week 12 , 36 ( 30 % ) patients in the erenumab had a 50 % or greater reduction from baseline in the mean number of monthly migraine days , compared with 17 ( 14 % ) in the placebo group ( odds ratio 2·7 [ 95 % CI 1·4 - 5·2 ] ; p=0·002 ) . The tolerability and safety profiles of erenumab and placebo were similar . The most frequent treatment-emergent adverse event was injection site pain , which occurred in seven ( 6 % ) participants in both groups . INTERPRETATION Compared with placebo , erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments . Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options . FUNDING Novartis Pharma Background Galcanezumab , a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide , has demonstrated in previous Phase 2 and Phase 3 clinical studies ( ≤6-month of treatment ) a reduction in the number of migraine headache days and improved patients ’ functioning . This study evaluated the safety and tolerability , as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine . Methods Patients diagnosed with episodic or chronic migraine , 18 to 65 years old , that were not exposed previously to galcanezumab , were r and omized to receive galcanezumab 120 mg or 240 mg , administered subcutaneously once monthly for a year . Safety and tolerability were evaluated by frequency of treatment-emergent adverse events ( TEAEs ) , serious adverse events ( SAEs ) , and adverse events ( AEs ) leading to study discontinuation . Laboratory values , vital signs , electrocardiograms , and suicidality were also analyzed . Additionally , overall change from baseline in the number of monthly migraine headache days , functioning , and disability were assessed . Results One hundred thirty five patients were r and omized to each galcanezumab dose group . The majority of patients were female ( > 80 % ) and on average were 42 years old with 10.6 migraine headache days per month at baseline . 77.8 % of the patients completed the open-label treatment phase , 3.7 % of patients experienced an SAE , and 4.8 % discontinued due to AEs . TEAEs with a frequency ≥ 10 % of patients in either dose group were injection site pain , nasopharyngitis , upper respiratory tract infection , injection site reaction , back pain , and sinusitis . Laboratory values , vital signs , or electrocardiograms did not show any clinical ly meaningful differences between galcanezumab dosesOverall mean reduction in monthly migraine headache days over 12 months for the galcanezumab dose groups were 5.6 ( 120 mg ) and 6.5 ( 240 mg ) . Level of functioning was improved and headache-related disability was reduced in both dose groups . Conclusion Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days . Safety and tolerability of the 2 galcanezumab dosing regimens were comparable . Trial registration Clinical Trials.gov as NCT02614287 , posted November 15 , 2015 . These data were previously presented as a poster at the International Headache Congress 2017 : PO-01 - 184 , Late-Breaking Abstract s of the 2017 International Headache Congress . ( 2017 ) . Cephalalgia , 37(1_suppl ) , 319–374 Background Patients with high-frequency episodic migraine ( HFEM ) have a greater disease burden than those with low-frequency episodic migraine ( LFEM ) . Acute treatment overuse increases the risk of migraine chronification in patients with HFEM . Galcanezumab , a humanized monoclonal antibody binding calcitonin gene-related peptide ( CGRP ) , is effective for migraine prevention with a favorable safety profile . Here , we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM . Methods Data were pooled from two double-blind , placebo-controlled phase 3 trials ; EVOLVE-1 and EVOLVE-2 . Patients were 18–65 years old , experienced 4–14 monthly migraine headache days ( MHDs ) for ≥1 year prior , with onset at < 50 years of age . Migraine headaches were tracked via electronic patient-reported outcome system and r and omization was stratified by low ( LFEM ; 4–7 monthly MHDs ) or high ( HFEM ; 8–14 monthly MHDs ) frequency . Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach . Results The intent-to-treat patients ( N = 1773 ) had a mean age of 41.3 years , were mostly white ( 75 % ) , female ( 85 % ) , and 66 % of patients had HFEM . In both the LFEM and HFEM subgroups , the overall ( Months 1–6 ) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg . Galcanezumab ( 120-mg and 240-mg ) significantly decreased the overall and monthly MHDs with nausea and /or vomiting , and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM . In both subgroups , the mean overall ( Months 1–6 ) and monthly percentages of patients with ≥50 % , ≥75 % , and 100 % reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo . Galcanezumab ( 120-mg and 240-mg ) significantly improved the Migraine-Specific Quality of Life Question naire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM . There were no significant subgroup-by-treatment interactions . Conclusions Galcanezumab was as effective in patients with HFEM as in those with LFEM . Associated symptoms , quality of life , and disability were similarly improved in patients with HFEM or LFEM.Trial registration NCT02614183 , NCT02614196 BACKGROUND We tested erenumab , a fully human monoclonal antibody that inhibits the calcitonin gene – related peptide receptor , for the prevention of episodic migraine . METHODS We r and omly assigned patients to receive a subcutaneous injection of either erenumab , at a dose of 70 mg or 140 mg , or placebo monthly for 6 months . The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month . Secondary end points were a 50 % or greater reduction in mean migraine days per month , change in the number of days of use of acute migraine – specific medication , and change in scores on the physical‐impairment and everyday‐activities domains of the Migraine Physical Function Impact Diary ( scale transformed to 0 to 100 , with higher scores representing greater migraine burden on functioning ) . RESULTS A total of 955 patients underwent r and omization : 317 were assigned to the 70‐mg erenumab group , 319 to the 140‐mg erenumab group , and 319 to the placebo group . The mean number of migraine days per month at baseline was 8.3 in the overall population ; by months 4 through 6 , the number of days was reduced by 3.2 in the 70‐mg erenumab group and by 3.7 in the 140‐mg erenumab group , as compared with 1.8 days in the placebo group ( P<0.001 for each dose vs. placebo ) . A 50 % or greater reduction in the mean number of migraine days per month was achieved for 43.3 % of patients in the 70‐mg erenumab group and 50.0 % of patients in the 140‐mg erenumab group , as compared with 26.6 % in the placebo group ( P<0.001 for each dose vs. placebo ) , and the number of days of use of acute migraine – specific medication was reduced by 1.1 days in the 70‐mg erenumab group and by 1.6 days in the 140‐mg erenumab group , as compared with 0.2 days in the placebo group ( P<0.001 for each dose vs. placebo ) . Physical‐impairment scores improved by 4.2 and 4.8 points in the 70‐mg and 140‐mg erenumab groups , respectively , as compared with 2.4 points in the placebo group ( P<0.001 for each dose vs. placebo ) , and everyday‐activities scores improved by 5.5 and 5.9 points in the 70‐mg and 140‐mg erenumab groups , respectively , as compared with 3.3 points in the placebo group ( P<0.001 for each dose vs. placebo ) . The rates of adverse events were similar between erenumab and placebo . CONCLUSIONS Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency , the effects of migraines on daily activities , and the use of acute migraine – specific medication over a period of 6 months . The long‐term safety and durability of the effect of erenumab require further study . ( Funded by Amgen and Novartis ; STRIVE Clinical Trials.gov number , NCT02456740 . BACKGROUND Calcitonin gene-related peptide ( CGRP ) is crucial in the pathophysiology of migraine . We assessed the safety , tolerability , and efficacy of ALD403 , a genetically engineered humanised anti-CGRP antibody , for migraine prevention . METHODS In this r and omised , double-blind , placebo-controlled , exploratory , proof-of-concept phase 2 trial , patients aged 18 - 55 years with five to 14 migraine days per 28-day period were r and omly assigned ( 1:1 ) via an interactive web response system to receive an intravenous dose of ALD403 1000 mg or placebo . Site investigators , patients , and the sponsor were masked to treatment allocation during the study . The primary objective was to assess safety at 12 weeks after infusion . The primary efficacy endpoint was the change from baseline to weeks 5 - 8 in the frequency of migraine days , as recorded in patient electronic diaries . Patients were followed up until 24 weeks for exploratory safety and efficacy analyses . Safety and efficacy analyses were done by intention to treat . This study is registered with Clinical Trials.gov , NCT01772524 . FINDINGS Between Jan 28 , 2013 , and Dec 23 , 2013 , of 174 patients r and omly assigned at 26 centres in the USA , 163 received either ALD403 ( n=81 ) or placebo ( n=82 ) . Adverse events were experienced by 46 ( 57 % ) of 81 patients in the ALD403 group and 43 ( 52 % ) of 82 in the placebo group . The most frequent adverse events were upper respiratory tract infection ( placebo 6 [ 7 % ] patients vs ALD403 7 [ 9 % ] patients ) , urinary tract infection ( 4 [ 5 % ] vs 1 [ 1 % ] ) , fatigue ( 3 [ 4 % ] vs 3 [ 4 % ] ) , back pain ( 4 [ 5 % ] vs 3 [ 4 % ] ) , arthralgia ( 4 [ 5 % ] vs 1 [ 1 % ] ) , and nausea and vomiting ( 2 [ 2 % ] vs 3 [ 4 % ] ) . Six serious adverse events were reported by three patients and were judged to be unrelated to study drug : in the ALD403 group , one patient had four serious adverse events and one had one serious adverse event , and in the placebo group , one patient had one serious adverse event . There were no differences in vital signs or laboratory safety data between the two treatment groups . The mean change in migraine days between baseline and weeks 5 - 8 was -5·6 ( SD 3·0 ) for the ALD403 group compared with -4·6 ( 3·6 ) for the placebo group ( difference -1·0 , 95 % CI -2·0 to 0·1 ; one-sided p=0·0306 ) . INTERPRETATION No safety concerns were noted with an intravenous dose of ALD403 1000 mg . This study also provides preliminary evidence for the efficacy of ALD403 in the preventive treatment of migraine in patients with a high monthly frequency of migraine days . FUNDING Alder Biopharmaceuticals |
490 | 12,036,237 | The literature was not evenly spread across different injury types and did not reflect the burden of injury .
There is a paucity of evidence relating to the prevention of child pedestrian injury .
Without such evidence , it remains difficult for those involved in health promotion to know how to design and target interventions to address inequalities in child injury rates | There is a known association between social deprivation and risk of death from unintentional injury in childhood .
In the UK context , these inequalities do not appear to be decreasing .
This paper reports on the findings of a systematic review of the world literature between 1975 and 2000 on the prevention of childhood injuries , with particular reference to social deprivation . | Objectives —To reduce fires and fire related injuries by increasing the prevalence of functioning smoke alarms in high risk households . Setting —The programme was delivered in an inner London area with above average material deprivation and below average smoke alarm ownership . The target population included low income and rental households and households with elderly persons or young children . Methods —Forty wards , averaging 4000 households each , were r and omised to intervention or control status . Free smoke alarms and fire safety information were distributed in intervention wards by community groups and workers as part of routine activities and by paid workers who visited target neighbourhoods . Recipients provided data on household age distribution and housing tenure . Programme costs were documented from a societal perspective . Data are being collected on smoke alarm ownership and function , and on fires and related injuries and their costs . Results —Community and paid workers distributed 20 050 smoke alarms , potentially sufficient to increase smoke alarm ownership by 50 % in intervention wards . Compared with the total study population , recipients included greater proportions of low income and rental households and households including children under 5 years or adults aged 65 and older . Total programme costs were £ 145 087 . Conclusions —It is possible to implement a large scale smoke alarm giveaway programme targeted to high risk households in a densely populated , multicultural , material ly deprived community . The programme 's effects on the prevalence of installed and functioning alarms and the incidence of fires and fire related injuries , and its cost effectiveness , are being evaluated as a r and omised controlled trial A prospect i ve study was design ed to evaluate the effects of education on the incidence of pediatric scald burns . Demographic data from our Trauma Registry identified the Zip code area of greatest risk . Eighty of 121 families with children in a large rental property were chosen r and omly for the education program . Twenty of these families also had an anti-scald device installed in the bathtub faucet ; all had two or more children under age 5 years . Families were surveyed before and after intervention . Safety knowledge improved post-education as judged by correct survey responses . Although 90 % of the families had water heaters set at " warm " ( < or = 120 degrees F ) , the actual temperature at the tap was above 130 degrees F in 71 % . The anti-scald devices did work , but at 9 months all but one had been removed because of sediment buildup , which prevented water flow . In the year of the study , the number of scald burns from the target Zip code area decreased from 15 to 12 . This was a pilot project for programs that can test public response to general safety education . An anti-scald device in conjunction with education works well in theory , but a better device needs to be engineered . In view of discrepancies between water heater setting s and tap water temperature , housing authorities could play a vital role in implementing safety measures Abstract Objective : To assess the effectiveness of safety advice at child health surveillance consultations , provision of low cost safety equipment to families receiving means tested state benefits , home safety checks , and first aid training on frequency and severity of unintentional injuries in children at home . Design : Cluster r and omised controlled trial . Setting : 36 general practice s in Nottingham . Subjects : All children aged 3 - 12 months registered with participating practice s. Interventions : A package of safety advice at child health surveillance consultations at 6 - 9 , 12 - 15 , and 18 - 24 months;provision of low cost safety equipment to families on means tested state benefits ; and home safety checks and first aid training by health visitors . Outcome measures : Primary outcomes measures were frequency and severity of medically attended injuries . Secondary outcome measures were self reported safety practice s , possession and use of safety equipment , knowledge and confidence in dealing with first aid , and perceptions of risk of injury and risk of hazards assessed by postal question naire at baseline and follow up at 25 months . Results : At baseline , both groups had similar risk factors for injury , sociodemographic characteristics , safety practice s , possession and use of safety equipment , knowledge and confidence in dealing with first aid , and perceptions of risk . No significant difference was found in frequency of at least one medically attended injury ( odds ratio 0.97 , 95 % confidence interval 0.72 to1.30 ) , at least one attendance at an accident and emergency department for injury ( , 0.76 to 1.37 ) , at least one primary care attendance for injury ( 0.75 , 0.48 to 1.17 ) , or at least one hospital admission for injury ( 0.69 , 0.42 to 1.12 ) . No significant difference in the secondary outcome measures was found between the intervention and control groups . Conclusions : The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home , and larger trials are required to assess the effect on more severe injuries Abstract Objective : To assess effectiveness of general practitioner advice about child safety , and provision of low cost safety equipment to low income families , on use of safety equipment and safe practice s at home . Design : R and omised , unblinded , controlled trial with initial assessment and six week follow up by telephone survey . Twenty families from intervention and control groups were r and omly selected for a home visit to assess validity of responses to second survey . Setting : A general practice in Nottingham . Subjects : 98 % ( 165/169 ) of families with children aged under 5 years registered with the practice . Interventions : General practitioner safety advice plus , for families receiving means tested state benefits , access to safety equipment at low cost . Control families received usual care . Main outcome measures : Possession and use of safety equipment and safe practice s at home . Results : Before intervention , the two groups differed only in possession of fireguards . After intervention , significantly more families in intervention group used fireguards ( relative risk 1.89 , 95 % confidence interval 1.18 to 2.94 ) , smoke alarms ( 1.14 , 1.04 to 1.25 ) , socket covers ( 1.27 , 1.10 to 1.48 ) , locks on cupboards for storing cleaning material s ( 1.38 , 1.02 to 1.88 ) , and door slam devices ( 3.60 , 2.17 to 5.97 ) . Also , significantly more families in intervention group showed very safe practice in storage of sharp objects ( 1.98 , 1.38 to 2.83 ) , storage of medicines ( 1.15 , 1.03 to 1.28 ) , window safety ( 1.30 , 1.06 to 1.58 ) , fireplace safety ( 1.84 , 1.34 to 2.54 ) , socket safety ( 1.77 , 1.37 to 2.28 ) , smoke alarm safety ( 1.11 , 1.01 to 1.22 ) , and door slam safety ( 7.00 , 3.15 to 15.6 ) . Stratifying results by receipt of state benefits showed that intervention was at least as effective in families receiving benefits as others . Conclusions : General practitioner advice , coupled with access to low cost equipment for low income families , increased use of safety equipment and other safe practice s. These findings are encouraging for provision of injury prevention in primary care . Key messages We assessed the effectiveness of general practitioner advice about child safety , and provision of low cost safety equipment to low income families , on safe practice s at home The intervention increased safe behaviour and use of safety equipment The intervention was equally effective in families receiving means tested benefits as in those not receiving benefits The effectiveness of this intervention should be evaluated over longer periods , in other practice s , and when delivered by other members of the primary healthcare In King County , Washington , during 1985 - 1986 , 98 children aged less than 15 years involved in pedestrian-motor vehicle collisions result ing in death or injuries severe enough to require hospitalization were identified through the Trauma Registry at the Regional Trauma Center and the Medical Examiner 's Office . Two age- and sex-matched controls were selected for each case , one through r and om digit dialing and the other from children undergoing appendectomy . Various environmental and traffic characteristics were ascertained from visits to the neighborhoods of all subjects . Children living in multifamily dwellings had a risk for injury that was 5.5 times greater than children living in single family homes ( 95 % confidence interval 2.5 - 12.3 ) . In general , areas with busier streets ( greater posted vehicle speeds and /or greater traffic volumes ) were associated with increased risk for pedestrian injuries . The lack of pedestrian crossing devices , crosswalks , or sidewalks , however , was not associated with an increased risk . When the analysis was restricted to the 23 cases injured in front of their homes and their controls , risks were not elevated for any of the street or traffic characteristics . The small size of the study and the lack of relevant information for many subjects limited our ability to adjust for the likely confounding influence of other household/environmental factors . Thus , these results should be viewed as suggestions for future investigations of the causes of childhood pedestrian injuries Abstract Objective : To apply a measure of exposure to injury risk for schoolchildren aged 11 - 14 across a population and to examine how risk factors vary with sex , age , and affluence . Design : Self completion question naire survey administered in schools in May 1990 . Setting : 24 schools in Newcastle upon Tyne . Subjects : 5334 pupils aged 11 - 14 , of whom 4637 ( 87 % ) completed the question naire . Results : Boys were exposed to greater risk than girls in journeys to places to play outdoors : they took longer trips and were more likely to ride bicycles ( relative risk 5.30 ( 95 % confidence interval 4.23 to 6.64 ) and less likely to travel by public transport or car . Younger pupils ( aged 11 - 12 ) were less exposed to traffic during journeys to and from school : their journeys were shorter , they were less likely to walk ( trip to school , relative risk 0.88 ( 0.83 to 0.94 ) , and they were more likely to travel by car ( trip to school , relative risk 1.33 ( 1.13 to 1.56 ) ) or school bus ( 1.33 ( 1.10 to 1.62 ) ) . Poorer children were exposed to greater risk than affluent children ( from families that owned a car and a telephone ) : they were less likely to travel to school by car ( relative risk 0.26 ( 0.20 to 0.33 ) ) or to be accompanied by an adult ( 0.39 ( 0.32 to 0.48 ) ) . Conclusion : Injury risk data can provide useful information on child injury prevention and can be used to identify priorities and target re sources for injury prevention on a citywide scale or for an individual school Objective —To evaluate the effectiveness of a skills training program in improving safe cycling behavior , knowledge , and attitudes in young children . Methods — Grade 4 children from six elementary schools in East York ( a borough of Metropolitan Toronto ) participated . The intervention — playground based instruction on bicycle h and ling skills by certified instructors — was r and omly allocated to three schools . Altogether 141 children participated : 73 in the intervention group and 68 in the control group , with follow up evaluations available on 117 ( 83 % ) . The primary outcome was safe cycling behavior ( straight line riding , coming to a complete stop , and shoulder checking before a left turn ) . A self report question naire collected data on knowledge and attitudes . Baseline assessment s were made in June , with follow up evaluations in September , 1995 . Results —The prevalence of safe cycling behaviors at follow up in the intervention and control groups respectively , were : straight line riding ( 90 % v 88 % ; p=0.782 ) , coming to a complete stop ( 90 % v 76 % ; p=0.225 ) , and shoulder checking ( 0 % v 2 % ; p=1.000 ) . Over time ( from baseline to follow up ) children in both groups were more likely to maintain straight line riding , less likely to ride on the sidewalk , and less likely to consider that a car had more right to the road . Conclusions —This brief skills training program was not effective in improving safe cycling behavior , knowledge , or attitudes among grade 4 children In a prospect i ve trial at two hospitals , 78 of 136 couples received a special 30-minute curriculum consisting of a lecture , a motion picture demonstrating the consequences of not using child car safety seats , and a question - and -answer session . Four to six months postpartum all parents were interviewed by telephone . When asked how their child rode during the most recent car trip , 96 % of parents who received the special curriculum said they used a crash-tested child car safety seat , compared with 78 % of those who had not received the curriculum . At hospital B , where parents reported demographic factors often associated with low compliance ( eg , lower income , low use of seat belts , lower educational level ) , compliance rose from 60 % before curriculum to 94 % after curriculum ( P<.01 ) . A car safety curriculum added to prenatal classes will increase parents ' use of child car safety seats . Obstetricians and those managing prenatal care should assume a role in educating expectant parents about child passenger safety . ( Obstet Gynecol 65:312 , 1985 HYPOTHESIS Young children can learn safety behavior in the public school system . These children will modify family seat belt use . SETTING DESIGN : This is a prospect i ve cohort analytic study conducted in a 50,000 square mile regionalized trauma center referral area . METHODS A school-based injury prevention program targeting kindergarten through second- grade ( K-2 ) students addressed four aspects of traffic safety : seat belt use , pedestrian and bicycle safety , school bus safety , and unsafe rides . After inservice instruction , teachers taught the program over a 10-week period . A simultaneous community traffic safety program was conducted through the media . Family seat belt use was monitored by blinded observation at six study schools and one control school . Income level of schools was characterized as low or high , based on student use of federal lunch subsidies . School program implementation was defined as good or poor , based on adherence to teaching protocol . RESULTS A total of 68,650 K-2 students have completed this traffic safety program during 1990 to 1994 . During the study year ( 1992 to 1993 ) , 25,900 students completed the program taught by 1,400 teachers in 95 schools . A total of 5,936 observations of seat belt use were made in seven schools . Income stratification delineated a subset of these schools in which seat belt use increased by 86 % ( p = 0.01 ) . Half of the schools failed to follow protocol , and no change in seat belt use was observed . CONCLUSIONS ( 1 ) School K-2 safety education improves family seat belt use , ( 2 ) low income schools should be targeted , and ( 3 ) strict adherence to the teaching protocol is essential OBJECTIVES Injury is a major US public health problem , particularly in urban minority communities . This paper evaluates the impact of the Safe Block Project , a comprehensive injury prevention trial , on home hazards and injury prevention knowledge in a poor urban African-American community . METHODS Nine census tracts in the community were allocated to either the intervention area or the control area . The intervention , carried out by trained community outreach workers , consisted of ( 1 ) home modification for simple prevention measures , ( 2 ) home inspection accompanied by information about home hazards , and ( 3 ) education about selected injury prevention practice s. Approximately 12 months after the intervention , r and om sample s of control and intervention homes were assessed for home hazards and injury prevention knowledge . RESULTS A significantly larger proportion of intervention homes than control homes had functioning smoke detectors , syrup of ipecac , safely stored medications , and reduced electrical and tripping hazards . No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct . CONCLUSIONS There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct . The Safe Block Project could serve as a model for future urban injury prevention efforts OBJECTIVE To examine , during the 3rd and 4th years of life , the health , development , rates of child maltreatment , and living conditions of children who had been enrolled in a r and omized trial of nurse home visitation during pregnancy and first 2 years of their lives . DESIGN Prospect i ve follow-up of families who had been r and omly assigned to nurse-visited and comparison conditions . SETTING Study conducted in semirural community in upstate New York . Families dispersed among 14 other states during 2-year period after children 's second birthdays . PARTICIPANTS Four hundred women were recruited through a health department antepartum clinic and offices of private obstetricians and were registered before 30th week of pregnancy . All women had no previous live births and 85 % were either teenaged ( < 18 years at registration ) , unmarried , or from Hollingshead social classes IV or V. Analysis focused on whites , who comprised 89 % of sample . INTERVENTION Nurse home visitation from pregnancy through second year of the child 's life . MAIN RESULTS There were no treatment differences in the rates of child abuse and neglect or children 's intellectual functioning from 25 to 48 months of age . Nurse-visited children , nevertheless , lived in homes with fewer hazards for children ; they had 40 % fewer injuries and ingestions and 45 % fewer behavioral and parental coping problems noted in the physician record ; and they made 35 % fewer visits to the emergency department than did children in the comparison group . Nurse-visited mothers were observed to be more involved with and to punish their children to a greater extent than were mothers in the comparison group . The functional meaning of punishment differed between the nurse-visited and comparison families . CONCLUSIONS The program does have enduring effects on certain aspects of parental caregiving , safety of the home , and children 's use of the health care system , but it may be necessary to extend the length of the program for families at highest risk to produce lasting reductions in child abuse and neglect Preventing children 's thermal injuries requires changes to both the home environment and the behaviour of family members . Two pilot studies were undertaken of a school-based programme that taught children aged 7 - 11 years about burns and scalds hazards , and encouraged changes to the home environment and family practice s through a take-home exercise . Both studies took place at ethnically diverse schools from low/middle-income areas of Waitakere City , New Zeal and . Study 1 involved 55 children who received the programme , and Study 2 involved 64 children who received the programme and 71 children from a control school . The children 's ability to identify the burns and scalds hazards illustrated in a series of pictures was measured before and after the programme . Children who received the programme showed considerable improvement in hazard identification at the post-test , while children at the control school showed minimal improvement . The take-home exercise was completed by 85 % of the children and their families in Study 1 , and 61 % of the participants from the intervention school in Study 2 . In both studies families reported positive safety changes as a result of the programme . The programme appeared equally effective with all the ethnic groups involved . Future development of the programme is discussed OBJECTIVE We have previously shown that an educational program was not effective in increasing bicycle helmet use in children of low-income families . The objective of this study was to evaluate a combined educational and helmet subsidy program in the same population , while controlling for secular trends . The secondary objective was to complete a third year of surveying children 's bicycle helmet use throughout the study community . DESIGN A prospect i ve , controlled , before- and -after study . SUBJECTS Bicycling children 5 to 14 years of age from areas of low average family income . SETTING A defined geographic community within a large urban Canadian city . INTERVENTION In April 1992 , students in three schools located in the area of lowest average family income were offered $ 10 helmets and an educational program ; three other low-income areas served as control areas . MAIN OUTCOME MEASURE Helmet use was determined by direct observation of more than 1800 bicycling children . RESULTS Nine hundred ten helmets were sold to a school population of 1415 ( 64 % ) . Reported helmet ownership increased from 10 % to 47 % . However , observed helmet use in the low-income intervention area was no different from the rate in the three low-income control areas ( 18 % versus 19 % ) . There was no difference in the trend in helmet use during the period of 1990 through 1992 in the intervention area ( 4 % to 18 % ) compared with the control areas ( 3 % to 19 % ) . Helmet use rates from all income areas have increased from 3.4 % in 1990 , to 16 % in 1991 , to 28 % in 1992 . In 1992 , helmet use in the high-income areas was 48 % and in the low-income areas was 20 % . CONCLUSIONS There has been a trend toward increasing helmet use in all income areas during the 3-year period . Despite encouraging helmet sales and increases in reported helmet ownership , the results of the observational study do not support the efficacy of a helmet subsidy program in increasing helmet use in children residing in areas of low average family income . Strategies to increase helmet use in children of low average family income remain a priority Objective —To evaluate the effectiveness of a multifaceted bicycle helmet promotion program for low income children attending preschool enrichment programs throughout Washington State . Study sample —Preschool Head Start programs that conducted routine home visits among their enrolled families at least five times during the school year were eligible . Eighteen sites and 880 children met this criterion and were able and willing to carry out evaluation activities . Two hundred children were from control sites where no helmet promotion activities were carried out . Intervention — Classroom activities with children , education of parents during school meetings and home visits , fitting and distribution of helmets , a bicycle skills and safety “ rodeo ” event , and requiring children to wear helmets while riding on school grounds . Evaluation methods —Regularly scheduled home visits were used to observe helmet use of enrolled preschool children before and after the promotion program . Home visitors requested parental permission for enrolled children to ride , and then noted whether the child wore a helmet . Results —Helmet use in the intervention group more than doubled , from 43 % to 89 % , while use in the control group increased from 42 % to 60 % ( p<0.05 for intervention group changes v control group changes ) . Conclusions —This multifaceted helmet promotion program successfully increased helmet use . Similar home visit protocol s may be useful to evaluate the impact of other injury intervention programs |
491 | 28,409,561 | We found that the most important side effects of PLD were skin toxicity and mucositis , but the proportion of patients who showed grade III and IV of these side effects was relatively low .
On the other h and , the occurrence of cardiotoxicity , the most important problem with doxorubicin , was considerably reduced in patients treated with PLD .
Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines , it has also new side effects .
However , it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC , especially in those with risk factors for cardiac diseases | Despite benefits of systemic chemotherapy in breast cancer treatment , several patients with early-stage breast cancer will develop metastatic breast cancer ( MBC ) .
Doxorubicin is among the most active agents against MBC .
However , the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity .
Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy .
Pegylated liposomal doxorubicin ( PLD ) is a product cl aim ed to achieve these two objectives because of its different pharmacokinetic profile .
The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials . | PURPOSE A multicenter phase II study to determine the activity and toxicity of Caelyx ( Doxil ; Sequus Pharmaceuticals Inc , Menlo Park , CA ) in patients with metastatic breast cancer . PATIENTS AND METHODS Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles . Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen . Fifty-two patients had disease at multiple sites . Hepatic and pulmonary disease were the predominant metastatic site in 50 patients . Response was assessable in 64 cases . RESULTS Sixteen patients achieved a partial response and a complete response ( overall response rate , 31 % ; ( 95 % confidence interval , 20 % to 43 % ) . Twenty patients ( 31 % ) had stable disease on treatment . Neutropenia > or = grade 3 occurred in 10 % of cycles ( 27 % of patients ) and mucositis > or = grade 3 in 10 % of cycles ( 32 % of patients ) . Significant alopecia was rare and routine prophylactic antiemetics were not required . At doses of 60 mg/m2 every 3 weeks , seven of 13 patients had > or = grade 3 skin toxicity ; overall , this toxicity complicated 25 % of treatment cycles . The incidence of > or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks , occurring in five of 32 patients and affecting only 5 % of 126 treatment cycles . CONCLUSION Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin . A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer . The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy |
492 | 15,689,610 | Given the limitation of evidence and the potential method ological weakness in the included study , it is valid to say that there is no evidence to recommend inclusion or exclusion of screening programs for oral cancer using visual examination in the general population . | Worldwide , oral cancer has one of the lowest survival rates .
It is well recognized that survival rates are improved if the disease is treated in its early stages .
The aim of this study was to assess the effectiveness of screening methods in decreasing the mortality of oral cancer . | BACKGROUND Approximately 3,000 new cases of oral cancer are diagnosed each year in Canada . Most of these cases occur among older adults with a history of tobacco use or excessive alcohol consumption . Preventive interventions for oral cancer include counselling of patients to modify risk factors and screening to identify precancerous and early-stage lesions . This report presents evidence -based guidelines on the prevention of oral cancer and precancer among asymptomatic patients . METHODS Literature search es of the 1966 - 1999 MEDLINE and CANCERLIT data bases were completed using the major MeSH heading mouth neoplasms . References from articles and recommendations of organizations were also review ed . The evidence -based methods of the Canadian Task Force on Preventive Health Care were used to assess evidence and to develop guidelines . Advice from experts and other recommendations were taken into consideration . RESULTS In cohort and case-control studies , smoking cessation decreased the risk of oral cancer and precancer . R and omized controlled trials ( RCTs ) indicate counselling by trained health care professionals is effective in promoting smoking cessation . Although counselling has been effective for the reduction of excessive alcohol consumption in RCTs , no studies have examined whether alcohol reduction reduces the risk of oral cancer or precancer . The usefulness of general population screening is limited by the low prevalence and incidence of the disease , the potential for false-positive diagnoses and the poor compliance with screening and referral . There is no evidence that screening of the general population or high-risk groups leads to a reduction in mortality or morbidity from oral cancer . INTERPRETATION There is good evidence to specifically consider smoking cessation counselling in a periodic health examination ( grade A recommendation ) . For population screening , there is fair evidence to specifically exclude screening for oral cancer ( grade D recommendation ) . For opportunistic screening during periodic examinations , there is insufficient evidence to recommend inclusion or exclusion of screening for oral cancer ( grade C recommendation ) . For patients at high risk , annual examination by physician or dentist should be considered . Risk factors include tobacco use and excessive consumption of alcohol . These recommendations are similar to those made by the Canadian Task Force on the Periodic Health Examination in 1994 and by the U.S. Preventive Services Task Force in 1996 A r and omized intervention trial is in progress in Kerala , India , to evaluate the effectiveness of oral visual inspection by trained health workers ( HWs ) in the prevention of oral cancer . Fourteen health workers with college graduation as the basic qualification were trained in oral visual inspection to identify oral cancers and precancers among the participants of the screening trial and to refer them for further confirmation and management . The aim of the present study was to evaluate the reproducibility and validity of the screening test provided by the health worker against the reference oral visual findings of three physicians . A total of 2069 subjects who had already been examined were re-examined by the health workers and physicians . The sensitivity and the specificity of the oral visual inspection were 94.3 % and 99.3 % respectively . There was moderate agreement between the findings of the initial and the repeat mouth examinations carried out by the health workers , which were on average 6 months apart . There was almost perfect agreement ( kappa = 0.85 ) between the findings of the health workers and the physicians in identifying the different types of oral precancerous lesions . The findings of our study indicate that it is possible to train re source persons to perform the oral cancer screening test as accurately as doctors , although experience appears to be a crucial component of health workers ' accuracy . The efficacy of such an approach to reduce the incidence of and mortality from oral cancer , however , remains to be proven Oral cancer is caused by chewing and smoking of tobacco . To assess the feasibility of primary prevention of oral cancer , two cohorts were studied in base-line surveys and then followed up annually for 10-yr in Ernakulam district of Kerala state . The intervention cohort consisted of 12212 tobacco users aged 15 yr and over , who were exposed to a concentrated program of education against tobacco use . The control cohort was a non-concurrent cohort of 6075 tobacco users studied using similar methods but with a minimal amount of advice against tobacco use . The stoppage of tobacco use increased and the incidence rate of leukoplakia decreased significantly and substantially in the intervention cohort compared to the control cohort . The decrease in the incidence of leukoplakia was indicative of the decrease in the risk of oral cancer since the two were intimately related . This study demonstrated feasibility of primary prevention of oral cancer A cluster r and omized controlled oral cancer screening trial is on-going in the Triv and rum district , India , to evaluate the efficacy of screening in reducing oral cancer mortality . Subjects , aged 35 years and above , in 13 clusters in the Triv and rum district , India , were r and omized to the intervention ( screening ) group ( 7 clusters , 78969 subjects ) to receive three rounds of screening by oral visual inspection by trained health workers at 3-year intervals or to a control group ( 6 clusters , 74739 subjects ) . Two rounds of screening were completed between 1995 and 2002 during which 69896 ( 88.5 % ) subjects were screened at least once , and 59.7 % of the 4408 screen-positive subjects were further investigated . In the intervention group , 344404 person-years were accrued and 329326 person-years were in the control group . In the intervention group , 149 incident oral cancer cases and 65 deaths from oral cancer were observed , and 106 incident cases and 62 deaths from oral cancer were observed in the control group . The programme sensitivity for detection of oral precancerous lesions and cancer was 81.5 % and the programme specificity was 84.8 % ; the programme positive predictive value was 39.6 % . In the intervention group 37.6 % of the cases were in stages I-II , as opposed to 18.9 % in the control group . The 3 year survival rate was 57.5 % in the intervention and 38.8 % in the control group ( P<0.05 ) . The age st and ardized oral cancer mortality rates were 21.2/100000 person-years in the intervention and 21.3/100000 in the control group . After completing two rounds of screening , oral cancer mortality rates were similar in both study groups It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia , erythroplakia and oral submucous fibrosis . One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions , with concurrent control of tobacco and alcohol use and other specific aetiological factors . However , the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known . We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster r and omised oral cancer screening trial in Kerala , India . Two-thirds of these revealed dysplasia on histology . After a minimum follow-up of 12 months ( range 12 - 37 months ) after surgical excision , 44 ( 74.8 % ) were remaining disease free with no evidence of recurrent/new lesions ; during follow-up , three ( 5 % ) developed new luekoplakic lesions , and six ( 10.1 % ) developed recurrent lesions , while six ( 10.1 % ) could not be traced after treatment . There was no event of malignant change during follow-up . The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1 % ( 95 % CI : 0.36 - 0.87 ) . Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia , since , as of now , the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established The aim of the study was to evaluate dental health care workers ' ability to recognise oral cancer and pre-cancer from colour photographic slides . A set of 80 slides was prepared , 40 were negative ( normal mucosa or lesions with no malignant potential ) and 40 were positive ( cancer or potentially malignant lesions ) . The slides were arranged in r and om order and projected in a st and ard format . The performance was evaluated in terms of mean sensitivity , specificity , mean correct score and likelihood ratio . There were no significant differences between the three groups of dentists ( consultants , juniors hospital dentists and general dentists ) , all performed better than the auxiliaries . The chances of a consultant making a correct decision were 5.5 times better than for an auxiliary and 2.7 times better than for a junior hospital dentist . The slide show enables a comparison of health care workers to be made and may be useful for the evaluation , training and calibration of examiners for an oral cancer screening programme BACKGROUND A study group composed of research ers from across the United States undertook a study to evaluate the sensitivity and specificity of OralCDx ( OralScan Laboratories Inc. ) , a computer-assisted method of analysis of the oral brush biopsy , in the detection of precancerous and cancerous lesions of the oral mucosa . METHODS The study group conducted a multicenter double-blind study comparing results of OralCDx analysis with those of scalpel biopsy of suspicious oral lesions , as well as using OralCDx on oral lesions that appeared benign clinical ly . RESULTS In 945 patients , OralCDx independently detected every case of histologically confirmed oral dysplasia and carcinoma ( sensitivity = 100 percent , false-negative rate = 0 percent ) . Every OralCDx " positive " result was subsequently confirmed by histology as dysplasia or carcinoma . The specificity for the OralCDx " positive " result was 100 percent , while the specificity for the OralCDx " atypical " results was 92.9 percent . In 4.5 percent of clinical ly benign-appearing lesions that would not have received additional testing or attention other than clinical follow-up , OralCDx uncovered dysplasia or carcinoma ( statistical sensitivity > 96 percent , P < .05 , n = 131 ; statistical specificity for the OralCDx " positive " result > 97 percent and for the " atypical " result > 90 percent , P < .05 , n = 196 ) . CONCLUSIONS The authors propose that this multicenter trial demonstrates that OralCDx is a highly accurate method of detecting oral precancerous and cancerous lesions . OralCDx can aid in confirming the nature of apparently benign oral lesions and , more significantly , revealing those that are precancerous and cancerous when they are not clinical ly suspected of being so . All OralCDx " atypical " and " positive " results should be referred for scalpel biopsy and histology to completely characterize the lesion . CLINICAL IMPLICATION S Given the difficulty in clinical ly differentiating premalignant and malignant lesions from benign lesions with a similar appearance , OralCDx appears to determine the significance of an oral lesion definitively and detect innocuous-appearing oral cancers at early , curable stages BACKGROUND Oral cancer screening procedures are design ed to collectively allow early detection of cancers in a body area accessible to visual and physical examination , as well as to facilitate timely treatment , awareness , and the ongoing education of the public . METHODS A state fair was selected for this activity because of the availability of a r and om population compatible with meeting these goals . A total of 1,151 individuals participated in this free elective activity . RESULTS Of this number 4.17 % were deemed to have oral pathologic states necessitating professional intervention , and 1.82 % were clinical ly diagnosed as having potential dysplastic or precancerous lesions . No clinical oral cancer was detected in this population . Nevertheless , by virtue of screening and detecting clinical ly premalignant lesions , the screening test advanced the diagnosis of potential oral cancers . CONCLUSIONS The outcome adds support to oral cancer screening as a procedure applicable in reducing morbidity and mortality from oral cancers Oral cancer satisfies the criteria for a suitable disease for screening , and oral visual inspection is a suitable test for oral cancer screening . The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated . The authors describe a cluster‐r and omized , controlled oral cancer screening trial in southern India and its early results The utilisation of primary health workers ( HWs ) for cancer control in developing countries has often been suggested , based on the experience of feasibility studies in India and Sri Lanka . We initiated a project in 1988 to evaluate the long-term feasibility of using trained HWs in secondary prevention of oral cancer , to bring about earlier detection of oral cancer in the communities served by them . Two hundred and eighty-two HWs attached to 14 primary health centres ( PHCs ) , serving approximately 0.92 million rural population in the northern half of Triv and rum district in Kerala , India , were trained in oral visual inspection to detect precancerous , malignant and other suspicious lesions of the oral cavity and refer them for confirmation and treatment . They were asked to examine subjects aged 35 years and above and to give person to person health education on tobacco in their target population . The HWs belonging to the PHCs serving approximately 1 million rural population in the southern half of Triv and rum district were not trained , and this region served as the control area . In addition to several process measures , stage distribution of oral cancer in subjects reporting from the intervention and control areas , as well as oral cancers referred by the HWs , as a proportion of total oral cancers from the intervention area , were the outcome measures evaluated . Only 9/282 ( 3.2 % ) trained HWs were motivated and they examined 17,812 eligible subjects in 3 years and referred 408 subjects with lesions ; 258/408 ( 63.2 % ) referred subjects reported for further examination and ten oral cancers were detected among them . ( ABSTRACT TRUNCATED AT 250 WORDS |
493 | 29,754,435 | Laparoscopic excision of endometriosis can improve QoSL . | INTRODUCTION Endometriosis is a benign disease that affects women of reproductive age .
Laparoscopic excision of endometriotic implants is considered one of the most effective therapeutic options .
The disease and its treatment can have a major impact on psychosexual well-being but this is often overlooked as most studies focus on pain instead of sexuality in a holistic approach .
The aim of this study was to review the current literature regarding the effect of laparoscopic surgery for endometriosis on quality of sexual life ( QoSL ) . | INTRODUCTION The concept of sexually related personal distress is currently central to the diagnosis of all female sexual dysfunctions ( FSD ) . In the current study , we have focused on validating a slightly revised version of the Female Sexual Distress Scale ( FSDS ) , the FSDS-Revised ( FSDS-R ) , to enhance the sensitivity of the instrument with patients suffering from hypoactive sexual desire disorder ( HSDD ) . In addition , we have attempted to extend the validation generalizability of the scale by demonstrating that both instruments possess reliability and discriminative validity in premenopausal women with HSDD . AIM To assess the validity of the revised version of the FSDS , the FSDS-R , for measuring sexual distress in women with HSDD . METHODS A prospect i ve method ological study carried out at 27 centers in North America enrolled 296 women aged 18 - 50 years with HSDD , another female sexual dysfunction ( FSD ) , or no FSD . The subjects completed the FSDS-R at baseline , day 7 , and day 28 , with a 30-day recall at baseline and with a 7-day recall on days 7 and 28 . MAIN OUTCOME MEASURES Receiver operating characteristic ( ROC ) analyses of FSDS , FSDS-R , and FSDS-R item 13 were used for the differentiation of HSDD from no FSD , while intraclass correlation coefficient ( ICC ) was used to estimate test-retest reliability . Cronbach 's coefficient alpha was used to measure the internal consistency of the FSDS-R and Pearson 's correlation coefficient to assess FSDS , FSDS-R , and FSDS-R item 13 with different recall periods ( 7 and 30 days ) . RESULTS Mean total FSDS , FSDS-R , and FSDS-R item 13 scores with either recall period were significantly higher ( P < 0.0001 ) in women with FSD or HSDD than in women with no FSD , showing both tests had discriminant validity . ROC analysis confirmed these findings , while an ICC of > 0.74 showed the test-retest reliability of both scales , including FSDS-R item 13 alone , and Cronbach 's coefficient alpha of > 0.86 confirmed the internal consistency of both tests . CONCLUSIONS Consistent with the FSDS , the FSDS-R demonstrated good discriminant validity , high test-retest reliability , and a high degree of internal consistency in measuring sexually related personal distress in women with HSDD . FSDS-R item 13 alone also demonstrated good discriminant validity and test-retest reliability OBJECTIVE To examine the effect on pain and quality of life for women with all stages of endometriosis undergoing laparoscopic surgery compared with placebo surgery . DESIGN A r and omized , blinded , crossover study . SETTING A tertiary referral unit in a district general hospital . PATIENT(S ) Thirty-nine women with histologically proven endometriosis completed the 12-month study . INTERVENTION(S ) Women were r and omized to receive initially either a diagnostic procedure ( the delayed surgical group ) or full excisional surgery ( the immediate surgery group ) . After 6 months , repeat laparoscopy was performed , with removal of any pathology present . MAIN OUTCOME MEASURE(S ) The end points were changes from baseline values of visual analogue pain scores , vali date d quality -of-life instruments ( EQ-5D and SF-12 ) , and sexual activity question naire scores . Patients and assessors of outcomes were blinded to the treatment-group assignment . RESULT ( S ) Significantly more of the 39 women operated on according to protocol reported symptomatic improvement after excisional surgery than after placebo : 16 of 20 ( 80 % ) vs. 6 of 19 ( 32 % ) ; chi(2)(1 ) = 9.3 . Other aspects of quality of life were also significantly improved 6 months after excisional surgery but not after placebo . Progression of disease at second surgery was demonstrated for women having only an initial diagnostic procedure in 45 % of cases , with disease remaining static in 33 % and improving in 22 % of cases . Nonresponsiveness to surgery was reported in 20 % of cases . CONCLUSION ( S ) Laparoscopic excision of endometriosis is more effective than placebo at reducing pain and improving quality of life . Surgery is associated with a 30 % placebo response rate that is not dependent on severity of disease . Approximately 20 % of women do not report an improvement after surgery for endometriosis STUDY QUESTION Is there a difference between women with endometriosis who underwent laparoscopic surgery with bowel resection or without bowel resection regarding depressive symptoms , relational adjustment and sexual functioning ? SUMMARY ANSWER Radical surgery for endometriosis in both groups improved the levels of depression and sexual functioning , but only the bowel resection patients showed improvements in relationship satisfaction . WHAT IS KNOWN ALREADY ? : The frequent pain symptoms in endometriosis patients can have an impact on psychological issues , relationships and sexual functioning . There are no data available on depression and relationship adjustment after endometriosis surgery . Sexual dysfunction problems have been described after bowel resection for rectal cancer , but no data are available for endometriosis surgery . STUDY DESIGN , SIZE , DURATION This prospect i ve cohort study included 203 consecutive women operated at the Leuven University Fertility Center ( LUFC ) between 1 September 2006 and 30 September 2008 for moderate ( n = 67 ) or severe ( n = 136 ) endometriosis . The preoperative response rate was respectively 84 % in the bowel resection group and 79 % in the no bowel resection group . PARTICIPANTS , SETTING , METHODS The beck depression inventory ( BDI ) measured depression , the dyadic adjustment scale ( DAS ) measured relationship satisfaction and the short sexual functioning scale ( SSFS ) measured sexual functioning before and 6 , 12 and 18 months after women had laparoscopic surgery at the LUFC , a tertiary referral centre for fertility exploration , treatment and surgery . MAIN RESULTS AND THE ROLE OF CHANCE Both groups had better post-operative outcomes when compared with the preoperative assessment s. Mean BDI and DAS levels were comparable with the normal population . Overall assessment points , the bowel resection patients had better outcomes for DAS ( P < 0.05 ) and SSFS ' arousal ' ( P < 0.05 ) than the no bowel resection patients . At 6 months after the operation , when compared with the no bowel resection group , the bowel resection group reported lower mean levels of BDI ( P < 0.05 ) , a lower incidence of SSFS ' pain during intercourse ' and ' orgasm problems ' ( P < 0.05 ) , and a lower proportion of patients with severe orgasm problems ( P < 0.05 ) . The data show that radical but fertility sparing surgery , with or without bowel resection , for the treatment of endometriosis results in comparable and good psychological outcomes concerning depression levels , relationship satisfaction and sexual functioning . LIMITATIONS , REASONS FOR CAUTION Although the initial response rate was good , response dropped over time and was significantly higher for bowel resection patients compared with the no bowel resection patients ( P = 0.05 ) . A responder/non-responder analysis for the whole study population showed no significant differences concerning pain problems . This reduces the possible risk of ( positive ) bias in the results . WIDER IMPLICATION S OF THE FINDINGS Endometriosis is a complex condition and the focus should not be on a one-dimensional end-organ gynaecological outcome , but should take into account the role of psychological factors in pain-related outcome . To this end , more prospect i ve data are needed on sexual functioning and psychological outcomes BACKGROUND Among subjects with endometriosis and deep dyspareunia ( DD ) , those with endometriosis of the uterosacral ligament ( USLE ) have the most severe impairment of sexual function . This study examines the effect of laparoscopic excision of endometriosis on DD and quality of sex life . METHODS This observational cohort prospect i ve study included 68 women with endometriosis suffering DD ( intensity of pain > or= 6 on a 10-cm visual analogue scale ) . Patients underwent laparoscopic full excision of endometriosis . Following surgery , they were asked to use nonhormonal contraception devices . Before surgery , at 6- and at 12-month follow-up , patients answered a self-administered question naire based on the Sexual Satisfaction Subscale of the Derogatis Sexual Functioning Inventory . RESULTS At 6- and 12-month follow-up , women with and without USLE had significant improvement in DD . Subjects with USLE reported increased variety in sex life , increased frequency of intercourse , more satisfying orgasms with sex , relaxing more easily during sex and being more relaxed and fulfilled after sex . Similar improvements were observed among women without USLE ; however , for some variables statistical significance was not reached . CONCLUSIONS Surgical excision of endometriosis improves not only DD but also the quality of sex life INTRODUCTION Deep infiltrating endometriosis ( DIE ) is a form of endometriosis in which the lesion penetrates for more than 5 mm under the peritoneal surface . It is a chronic disease which can impair women 's sexual function . There is a growing body of evidence supporting combined surgical/medical treatment in the management of DIE . AIMS The aims of this article are to evaluate the impact of the laparoscopic full excision of endometriosis and postoperative combined oral contraceptives ( COC ) administration on sexual function in patients with DIE and to compare sexual function outcomes of women su bmi tted to intestinal resection and nodule excision . METHODS It is a prospect i ve cohort study in a tertiary care university hospital on 106 sexually active women , with histologically confirmed DIE , managed by laparoscopy and subsequent COC therapy for 6 months . Patients filled preoperatively and 6-month postoperatively a quality of sexual life question naire , the Sexual Health Outcomes in Women Question naire ( SHOW-Q ) and they ranked their symptom intensity using a 10-point visual analogue scale ( VAS ) . MAIN OUTCOME MEASURES Sexual function was measured through the SHOW-Q scores and pain symptoms through VAS scores . Intraoperative details , type of intervention and perioperative complications were noted . RESULTS Six months after surgery and postoperative COC treatment , a significant improvement was observed in the SHOW-Q domains of pelvic problem interference , sexual satisfaction and desire ( P<0.05 ) . Laparoscopic management of DIE did not change significantly the orgasm area of the sexual functioning ( P=0.7 ) . No significant difference was found in SHOW-Q scores between patients su bmi tted to intestinal resection and patients su bmi tted to intestinal nodule excision ( P>0.05 ) . CONCLUSIONS Sexual desire , satisfaction with sex and pelvic problem interference with intercourse are significantly improved after 6 months from laparoscopic excision of DIE combined with postoperative COC therapy . No difference in sexual outcomes was detected between patients su bmi tted to intestinal resection and nodule excision OBJECTIVE To identify prognostic factors for pain and endometrioma recurrence after complete laparoscopic excision of endometrioma(s ) . DESIGN Prospect i ve observational study . SETTING Tertiary care university hospital . PATIENT(S ) One-hundred sixty-six consecutive women affected by uni- or bilateral ovarian endometrioma(s ) . INTERVENTION(S ) Laparoscopic conservative treatment of endometriosis . MAIN OUTCOME MEASURE(S ) Patient demographic characteristics , surgical findings , and surgical results were prospect ively recorded . Postoperative follow-ups were carried out every 3 months to identify pain and /or endometrioma recurrence for a minimum of 3 years . RESULT ( S ) Dysmenorrheal , dyspareunia , and chronic pelvic pain recurred in 14.5 % , 6 % , and 5.4 % of women , respectively . Prior surgery for endometriosis , adhesion extension , and use of ovarian stimulation drugs ( OSD ) were unfavorable prognostic factors for pain symptoms . Ovarian endometrioma recurred in 9.6 % of cases ; negative factors were prior surgery for endometriosis , OSD , pelvic adhesions , and high American Society for Reproductive Medicine disease scores . Postoperative pregnancy showed a significant protective effect on pain and disease recurrences . CONCLUSION ( S ) Prior surgery , presence of adhesions , and ovulation drugs are negative prognostic factors . Pregnancy has a protective effect on disease and pain recurrence Two hundred and forty‐two postmenopausal women between 35 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and r and omly allocated to treatment either with transdermal estradiol therapy ( Estraderm * 50 μg/24 h ) ( E ) or placebo ( P ) . The patches were changed twice a week and treatment continued for 12 weeks . No progestogen supplement therapy was given during the study . No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than sin months ago . As a part of a larger study assessing women 's quality of life , a Swedish version of ‘ McCoy 's Sex Scale Question naire ’ was administered at the start of treatment and after 12 weeks . This question naire contains nine items regarding different aspects of sexual life . The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared . Items regarding ‘ satisfaction with frequency of sexual activity , sexual fantasies . degree of enjoyment . vaginal lubrication and pain during intercourse ’ were positively influenced in the E group compared to the P group . Items not affected were ‘ frequency of orgasm and sexual arousal ’ . A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life question naires OBJECTIVE The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a r and omized trial over 12 weeks . STUDY DESIGN Two hundred forty-two women were r and omized , and 223 were analyzed for efficacy ( n = 112 for estradiol and n = 111 for placebo ) . The quality of life was assessed by means of a battery of st and ard question naires . RESULTS Quality of life improved after both therapies , but health-related quality of life ( p = 0.0003 ) and well being ( p = 0.003 ) improved more after transdermal estradiol therapy than after placebo . This was also the case for all specific climacteric aspects , including sexual problems ( p < 0.0001 ) and dysfunction ( p = 0.01 ) , at comparison with placebo . Self-rated symptom relief was more pronounced with estrogen therapy than with placebo ( p < 0.0001 ) . CONCLUSION It was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life This observational cohort study examined the effect of laparoscopic full excision of endometriosis combined with postoperative triptorelin treatment on deep dyspareunia ( DD ) and quality of sex life . One year after completing the postoperative treatment , 45.9 % of the patients had no DD and 34.7 % reported a decrease in DD intensity ; an increase in the frequency of sexual intercourse was reported by 62.2 % of the women ; objective improvements in several aspects of sex life were observed BACKGROUND This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis . METHODS In this prospect i ve observational cohort study , 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis . Of these , 216 women underwent surgical assessment and 176 were confirmed to have endometriosis . Question naires and visual analogue scale ( VAS ) scores for dysmenorrhoea , non-menstrual pelvic pain , dyspareunia and dyschesia as well as quality of life instruments ; the EQ-5Dindex and EQ-5Dvas , Short-Form 12 ( SF-12 ) and sexual activity question naires were completed pre-operatively . Intra-operative details of revised American Fertility Society ( rAFS ) stage , site of disease , associated tests , duration of surgery and complications were noted . Follow-up was performed by postal question naire and chart review . For women who had further surgery , rAFS stage , site of disease , other procedures and histology were all recorded . RESULTS Pain scores were all significantly reduced at 2 - 5 years for dysmenorrhoea ( median VAS baseline versus follow-up 2 - 5 years ) ; 9 versus 3.3 ( P < 0.0001 ) , non-menstrual pelvic pain 8 versus 3 ( P < 0.0001 ) , dyspareunia 7 versus 0 ( P < 0.0001 ) and dyschesia 7 versus 2 ( P < 0.0001 ) . Quality of life was improved for the EQ-5Dindex ( P = 0.008 and the EQ-5Qvas ( P = 0.03 ) and for sexual function with pleasure ( P = 0.001 ) and habit ( P = 0.012 ) being improved and discomfort being decreased ( P = 0.001 ) . The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36 % . A rAFS score of > 70 was predictive of requiring further surgery ( P = 0.03 ) . Of women who had further surgery , endometriosis was found histologically in 68 % . CONCLUSIONS Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years . The probability of requiring further surgery is 36 % . Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence OBJECTIVE The aim of the current study was to evaluate the effect of surgical removal of endometriosis on dyspareunia , sexual function , quality of sex life and interpersonal relationships . STUDY DESIGN A question naire-based multicentre prospect i ve study was conducted in six tertiary referral centres in Austria and Germany . Ninety-six patients with histologically proven endometriosis and dyspareunia were included . Before surgery and averagely 10 months postoperatively ( range 9 - 12 months ) , the Female Sexual Function Index ( FSFI ) and the Female Sexual Distress Scale ( FSDS ) were used to screen women 's sexuality . Additionally , we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered question naire . RESULTS Pain scores measured via NAS during/after intercourse decreased significantly after surgery . Frequencies of interrupted sexual intercourse , feelings of guilt towards the partner , being afraid of pain before/during sexual intercourse and feelings of being a burden for the relationship also decreased significantly in patients with peritoneal endometriosis and deep infiltrating endometriosis . Interestingly , sexually related personal distress did not improve in women with peritoneal endometriosis/vaginal resection , but improved in cases of deep infiltrating endometriosis ( DIE ) . CONCLUSION Radical laparoscopic excision of endometriosis offers an effective treatment option and offers a significant improvement in dyspareunia and quality of sex life STUDY OBJECTIVE To describe the effect of fertility-sparing laparoscopic excision of endometriosis and bowel resection on clinical and quality -of-life outcomes . DESIGN Prospect i ve observational cohort study ( Canadian Task Force classification II-2 ) . SETTING Australian tertiary referral center for the surgical treatment of endometriosis . PATIENTS Seven consecutive patients with known endometriosis involving the bowel . INTERVENTION Laparoscopic resection of all endometriosis , including laparoscopic bowel resection with end-to-end anastomosis with or without temporary ileostomy . MEASUREMENTS AND MAIN RESULTS Preoperative and 12-month postoperative data were collected by use of visual analogue scores for dysmenorrhea , nonmenstrual pelvic pain , dyspareunia , and dyschezia . Vali date d research tools ( SF12 , EuroQOL , and Sexual Activity Question naire ) also assessed quality of life . Reduction in median pain scores at baseline was demonstrated and at 12 months after operation for dysmenorrhea 71 ( interquartile range 43 - 85 ) versus 5 ( 0 - 10 ) ; p=.028 , nonmenstrual pelvic pain 74 ( 48 - 85 ) versus 11 ( 0 - 18 ) ; p=.046 , dyspareunia 66 ( 0 - 98 ) versus 5 ( 0 - 8 ) ; p=.080 , and dyschezia 48 ( 20 - 64 ) versus 20 ( 0 - 40 ) ; p=.173 . All measures of quality of life were improved at 12 months after surgery , although not reaching statistical significance because of the small sample size . All three women wishing to conceive after operation have been successful , result ing in three live births at term . There were few complications associated with this surgery . CONCLUSION Fertility-sparing laparoscopic excision of endometriosis with bowel resection results in improvements in all aspects of pain and quality of life . Results appear to parallel published data for conservative resection of endometriosis not involving bowel . For women with severe endometriosis involving bowel , this surgical treatment provides a viable alternative to pelvic clearance and successfully maintains fertility BACKGROUND Endometriosis is a chronic and progressive condition of women of reproductive age . It is strongly associated with significant impairment of sexual function . AIM To objective ly evaluate the impact of laparoscopic excision of endometriosis on sexual function in patients with deep infiltrating endometriosis ( DIE ) compared to healthy women . SETTING AND DESIGN Prospect i ve study , including 250 patients with a diagnosis of DIE scheduled for laparoscopic surgery and 250 healthy women . METHODS A sexual activity question naire , SHOW-Q ( Sexual Health Outcomes in Women Question naire ) , was used to collect data pertaining to women 's satisfaction , orgasm , desire and pelvic problem interference with sexual function . Women with DIE underwent complete excision of endometriotic lesions . All participants were asked to complete the SHOW-Q question naire before and after surgery . RESULTS SHOW-Q scores in the endometriosis group before and 6 months after surgery were compared with the healthy group scores . A significant improvement was found between pre- and post-treatment in the scores of the satisfaction scale , desire scale and pelvic problem interference scale of SHOW-Q. The distribution of post-surgery SHOW-Q scores was comparable to healthy women 's scores apart from the orgasm scale score , which was unchanged in the post-surgery group . CONCLUSIONS The surgical approach to treatment has a positive impact not only on organ impairment but also on sexual function in women affected by DIE Aim Endometriosis is relatively common condition in fertile women and may affect the alimentary tract . Laparoscopic rectosigmoid resection for endometriosis has been found to be both feasible and safe . The aim of the present study was to prospect ively evaluate the quality of life and sexual function of patients who have undergone rectosigmoid resection for endometriosis STUDY OBJECTIVE Endometriosis can affect 10 % of women at reproductive age . Of those , 5.3 % to 12 % will have endometriosis affecting the bowel . Although outcomes after surgery for severe endometriosis affecting the bowel have previously been studied and have shown improvement in generic quality of life indices and sexual function , few studies have evaluated bowel function or symptoms specific to endometriosis . Our aim was to determine the quality of life after radical excision of rectovagina endometriosis compromising the bowel . DESIGN Single-center prospect i ve cohort study ( Canadian Task Force classification II-2 ) . SETTING Specialist referral center for the management of advanced endometriosis . PATIENTS Women with severe rectovaginal endometriosis compromising the bowel . INTERVENTIONS Comparison of preoperative data with a 2- , 6- , and 12-month follow-up was made for consecutive patients who underwent surgery for endometriosis with bowel involvement . The main outcome measures were quality of life using the Endometriosis Health Profile 30 and EuroQol-5 dimension question naires . Bowel symptoms were measured using the Gastrointestinal Quality of Life Index . Dysmenorrhea , dyspareunia , dyschezia , and chronic pain were measured using a visual analogue scale . To compare preoperative and postoperative scores , a Freidman test was performed followed by a preoperative and 12-month postoperative Wilcoxon signed-rank test . A Mann-Whitney U test was used to compare the results between those who had pelvic clearance and those who did not . MEASUREMENTS AND MAIN RESULTS In total , 137 patients had surgery , of which 100 completed follow-up to 12 months . The serious perioperative and postoperative complication rate was 7.3 % . The results show significant improvement in almost all variables measured ( p < .01 ) . At 12 months patients who had a pelvic clearance ( hysterectomy with bilateral salpingo-oophorectomy ) had significantly less pain with better bowel function . Additionally , they had higher quality of life scores and greater satisfaction with their treatment . There was no significant difference between any postoperative variables tested regardless of the type of bowel surgery . CONCLUSION Severe rectovaginal endometriosis compromising the bowel can be treated surgically with experienced combined gynecologic and colorectal input with a low serious complication rate . Surgery by an experienced multidisciplinary team results in significant improvement in pain , sexual function , and quality of life up to 1 year postoperatively . Pelvic clearance improves outcome and patients should be counseled accordingly . There is no difference in outcome between the types of bowel surgery undertaken as long as all visible/palpable endometriosis is removed Objective : To assess the clinical outcome of women requiring laparoscopic excision of moderate-severe endometriosis in women with and without bowel resection and reanastomosis . Methods : Two hundred three patients with laparoscopically excised moderate ( n = 67 ) or severe ( n = 136 ) endometriosis ( rAFS : revised endometriosis classification of the American Fertility Society ) were prospect ively followed during a median of 20 months ( 1–45 months ) using a CONSORT-inspired checklist . Patients completed the EHP30 Quality -of-Life Question naire and visual analogue scales ( VAS ) for dysmenorrhea , chronic pelvic pain , and deep dyspareunia and answered questions about postoperative complications , re interventions /recurrences , and fertility outcome 1 month before and 6 , 12 , 18 , and 24 months after surgery . Clinical outcome was compared between women with deeply infiltrative endometriosis undergoing CO2 laser ablative surgery with bowel resection ( study group , 76/203 ; 37 % ) and without bowel resection ( control group , 127/203 ; 63 % ) . Results : Both groups were similar with respect to population characteristics and clinical outcome , except for mean rAFS score [ higher in study group ( 73 ± 31 ) than in control group ( 48 ± 26 ) ] and minor complication rate [ higher in study group ( 11 % ) than in control group ( 1 % ) ] . In both groups , mean VAS and EHP30 scores improved significantly and remained stable for 24 months after surgery , with a pregnancy rate of 51 % . Within 1 , 2 , and 3 years follow-up , the cumulative reintervention rate was 1 % , 7 % , and 10 % , respectively , and the cumulative endometriosis recurrence rate was 1 % , 6 % , and 8 % , respectively . Conclusions : Clinical outcome after CO2 laser laparoscopic excision of moderate-severe endometriosis was comparable in women with or without bowel resection and reanastomosis , except for a higher minor complication rate occurring in women with bowel resection and reanastomosis ( NCT00463398 ) Objective . To evaluate sexual function , quality of life and pelvic pain after endometriosis surgery including vaginal resection . Design . Prospect i ve observational study with 12 months follow up . Setting . Regional central hospital and university hospital . Population . Twenty‐two patients with deep endometriotic nodules in the posterior fornix of the vagina undergoing complete excision of endometriosis , including vaginal resection . Methods . Sexual functioning was measured with the McCoy Female Sexuality Question naire , quality of life with a generic question naire ( 15D ) and pain with a 10‐point visual analog scale . Question naires were completed before and 12 months after the surgery . Main outcome measures . Changes in sexual function scores , quality ‐of‐life scores and pain . Results . Twelve months after surgery , the sexual satisfaction score was higher ( p= 0.03 ) and the sexual problems score lower ( p= 0.04 ) compared with baseline values . Health‐related quality ‐of‐life scores for discomfort and symptoms ( p= 0.001 ) , distress ( p= 0.04 ) , vitality ( p= 0.03 ) and sexual activity ( p= 0.001 ) , and the overall 15D score ( p < 0.001 ) , were significantly improved . The severity of all studied types of pain was significantly decreased ( p < 0.05 ) . Conclusions . Complete excision of endometriosis , including vaginal resection , seems to offer a significant improvement in sexual functioning , quality of life and pelvic pain in symptomatic patients with deeply infiltrating endometriotic nodules in the posterior fornix of the vagina . This surgery may be associated with complications and adverse new‐onset symptoms , and should be performed only after thorough consultation with the patient |
494 | 25,743,996 | Conclusion Our analysis identified several clinicopathologic factors associated with AL in patients who underwent LAR .
The knowledge of these risk factors may influence treatment- and procedure-related decisions and possibly reduce the leakage rate | Background Anastomotic leakage ( AL ) is a serious complication in laparoscopic rectal cancer surgery , and risk factors for AL are not well defined .
Herein , we conducted a systematic review to quantify the clinicopathologic factors predictive for AL in patients who underwent laparoscopic anterior resection ( LAR ) for rectal cancer . | Purpose : This study evaluated the risk factors for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique . Methods : The total prospect i ve registry of 111 patients with rectal cancer who initially underwent laparoscopic low anterior resection using a stapling technique was review ed . Univariate and multivariate analyses were carried out to identify relevant risk factors . Results : Overall anastomotic leakage rate was 5.4 % ( 6/111 ) . Univariate analysis demonstrated that body mass index ( BMI ) ( P=0.0377 ) was significantly associated with anastomotic leakage . After univariate analysis , the variables of BMI and the size of the circular stapler ( P=0.0923 ) were selected for multivariate analysis , as their P values were < 0.2 , and multivariate analysis demonstrated that BMI was independently predictive of developing anastomotic leakage ( P=0.0458 ) . Conclusions : Laparoscopic surgery for rectal cancer using a stapling technique can be performed safely without increasing the risk of anastomotic leakage , and increased BMI might be a potential risk factor for anastomotic leakage Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery PURPOSE : This study was design ed to identify the clinical features of anastomotic leakage after laparoscopic resection of rectal cancer and to evaluate the outcomes of laparoscopic management for this problem . METHODS : Prospect ively collected data were obtained from 307 patients with rectal cancer who underwent laparoscopic proctectomy and primary anastomosis . Age , sex , tumor location , tumor stage , body mass index , comorbidities , ileostomy , conversion , intraoperative blood loss , operative time , previous abdominal operation , and hospital stay were analyzed for patients with or without anastomotic leakage . Management and outcome of anastomotic leakage also were analyzed . RESULTS : Anastomotic leakage occurred in 29 patients ( 9.4 percent ) . Diverting ileostomy was initially fashioned in 65 patients ( 21.2 percent ) . Leakage was related to young age , male sex , lower tumor location , and longer operation time . Ten patients ( 34.5 percent ) were successfully managed with conservative treatment . Seventeen patients ( 58.6 percent ) were managed via a laparoscopic approach . Open surgery was performed in two patients who showed diffuse fecal soiling or had previous conversion , respectively . There was no mortality . CONCLUSIONS : When leakage occurs , laparotomy or colostomy is not needed routinely . For surgical intervention , the abdominal cavity should be explored first by laparoscopic visualization because the majority of patients can be successfully managed with laparoscopy and ileostomy BACKGROUND Animal studies have documented significantly better preserved postoperative cell-mediated immune function , as measured by serial delayed-type hypersensitivity ( DTH ) challenges , after laparoscopic-assisted than after open bowel resection . Similarly , in humans , the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses ; whereas after laparoscopic cholecystectomy , no significant change in DTH response has been noted . The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy . METHODS A total of 35 subjects underwent either laparoscopic ( n = 18 ) or open colectomy ( n = 17 ) in this prospect i ve but not r and omized study . Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study . DTH challenges were carried out at three time points in all patients : preoperatively , immediately following surgery , and on the third postoperative day ( POD 3 ) . Responses were measured 48 h after each challenge and the area of in duration calculated . There were no significant differences between the laparoscopic ( LC ) and open ( OC ) colorectal resection groups in regard to demographics , indications for surgery , or type of resection carried out . The percentage of patients transfused was similar in both groups ( 17 % , LC ; 12 % OC ; p = NS ) . In the LC group , all cases were completed without conversion using minimally invasive methods . There were no perioperative deaths , and the rate of postoperative complications was similar in both groups . The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods . RESULTS In regards to the OC group results , the median sum-total DTH responses for the day of surgery challenges ( 0.44 + /- 69 cm2 ) and the POD 3 challenges ( 0.72 + /- 3.37 cm2 ) were significantly smaller than the preoperative results ( 3.61 + /- 3.83 cm2 , p < 0.0005 vs op day and p < 0.0003 vs POD 3 results ) . When the LC group results were similarly analyzed , no significant difference in DTH response was noted between the pre- and the postoperative challenge results . Additionally , when the median percent change from baseline was calculated and considered for the OC group 's DTH results , both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results ( vs day of surgery , p < 0.007 ; vs POD 3 , p < 0.006 ) . Similar analysis of the LC group 's results yielded nonsignificant differences between the pre- and postoperative responses . Lastly , when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges , a significant difference was noted for the POD 0 challenge ( LC , -21 % ; OC 88 % ; p < 0.004 ) but not for the POD 3 challenge . CONCLUSIONS The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses . This was not the case for the laparoscopic group ( a combination of fully laparoscopic and laparoscopic-assisted resections ) . When the open and laparoscopic groups results are directly compared , regarding the results of the day of surgery DTH challenges , the LC groups median percent change from baseline was significantly less than that observed in the OC group . These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively , whereas in this study laparoscopic colorectal resection was not . Further human studies are needed to verify these findings and to determine the clinical significance , if any , of this temporary difference in immune function following colon resection Anastomotic leakage is a major complication of rectal cancer surgery . The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision ( TME ) Purpose The anastomotic leakage rate after rectal resection has been reported to be approximately 2.5 - 21 percent , but most results were associated with open surgery . The aim of this study was to identify risk factors and their relationship to the experience of the surgeon for anastomotic leakage after laparoscopic rectal resection . Methods Between March 2003 and December 2008 , 156 patients underwent a laparoscopic rectal resection without a diverting ileostomy . The patients ' characteristics , the details of treatment , the intraoperative results , and the postoperative results were recorded prospect ively . Univariate and multivariate analyses were applied to identify risk factors for anastomotic leakage . Results The majority of operations were performed for malignant disease ( n = 150 ; 96.2 % ) , and 96 patients ( 61.5 % ) were males . Conversion to open surgery occurred in 1 case ( 0.6 % ) . The anastomotic leak rate was 10.3 % ( 16/156 ) , and there were no mortalities . In the univariate analysis , tumor location , anastomotic level , intraoperative events , and operation time were associated with increased anastomotic leakage rate . In the multivariate analysis , anastomotic level ( odds ratio [ OR ] , 6.855 ; 95 % confidence interval [ CI ] , 1.271 to 36.964 ) and operation time ( OR , 8.115 ; 95 % CI , 1.982 to 33.222 ) were significantly associated with anastomotic leakage . Conclusion The important risk factors for anastomotic leakage after laparoscopic rectal resection without a diverting ileostomy were low anastomosis and long operation time . An additional procedure , such as diverting stoma , may reduce the anastomotic leakage if it is selectively applied in cases with these risk factors BACKGROUND Laparoscopic rectal transection carries the risk of anastomotic leakage because of its technical difficulty and long staple line with an inadequate cutting angle . Our objective was to investigate the risk factors affecting anastomotic leakage after laparoscopic intracorporeal colorectal anastomosis with a double stapling technique . STUDY DESIGN Between November 2006 and September 2008 , 270 consecutive patients underwent laparoscopic sigmoidectomy and anterior resection with double stapling technique for distal sigmoid and rectal cancer . Data were collected prospect ively . Univariate and multivariate analyses were performed to determine risk factors for anastomotic leakage . Additionally , we evaluated the relationship between the number of stapler firings and clinical parameters . RESULTS Anastomotic leakage was noted in 17 ( 6.3 % ) of 270 patients . In univariate analyses , tumor location ( p = 0.021 ) , operation time ( p = 0.025 ) , number of stapler firings ( p = 0.040 ) , and diameter of the circular stapler ( p = 0.022 ) were significant risk factors for anastomotic leakage . Multivariate analyses showed that middle or lower rectal cancer was an independent factor affecting anastomotic leakage ( p = 0.013 ) . The number of stapler firings increased significantly in men ( p = 0.023 ) , in patients with a tumor at a lower level ( p = 0.034 ) , and in those with longer operation times ( p < 0.001 ) . CONCLUSIONS A reduction in the number of linear stapler firings is necessary to avoid anastomotic leakage after laparoscopic colorectal anastomosis with a double stapling technique . We recommend that a diverting ileostomy is m and atory in patients with middle and lower rectal cancer where multiple linear staplers were used Background This study aim ed to prospect ively evaluate operative safety and mid-term oncologic outcomes of laparoscopic rectal cancer resection performed by a single surgeon . Methods Three hundreds twelve patients ( male , 181 ) were enrolled in this analysis . 257 patients ( 82.4 % ) had tumors located below 12 cm from the anal verge . Distribution of TNM stages was 0:I : II : III : IV = 4.2%:17.9%:32.4%:37.2%:8.3 % . 225 patients ( 71.1 % ) had T3/T4 lesions . Pre- and post-operative radiation was given in 6 and 20 patients , respectively . Results Sphincter-preserving operation was performed in 85.9 % . Mean operating time was 212 minutes . Conversion rate was 2.6 % . Overall morbidity rate was 21.1 % . Anastomotic leakage occurred in 6.4 % . Operative mortality rate was 0.3 % . Mean number of harvested nodes was 23 . Mean distal tumor-free margin was 2.8 cm . The circumferential resection margin was positive in 13 patients ( 4.2 % ) . With a mean follow-up of 30 months in the stage I – III patients , the local recurrence rate was 2.9 % . Systemic recurrence occurred in 11.7 % . No port-site recurrence was observed . Conclusion Laparoscopic resection of rectal cancer provided safe operative parameters and adequate mid-term oncologic outcomes . When considering a high volume of advanced and low-lying cancers but rather narrow indication to radiotherapy , the 2.9 % local recurrence rate seems promising data . Long-term follow-up is m and atory to draw conclusion INTRODUCTION Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality . The long-term prognosis of anastomotic leakage is poorly documented . This study was design ed to assess whether anastomotic leakage affects five-year survival and local recurrence . METHODS A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 ( prospect i ve data , 5-year follow-up ) . The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test . RESULTS A total of 1,834 patients underwent a curative resection with an anastomosis ( anastomotic leak = 71 ; 3.9 percent ) : 30-day mortality : 18.3 percent in the leak group , and 3.5 percent in the nonleak group ( P < 0.001 ) ; local recurrence : 19 percent in the leak group , and 9.8 percent in the nonleak group ( P = 0.018 ) . A total of 1,201 patients underwent colonic anastomosis ( anastomotic leak = 31 ; 2.6 percent ) . There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups . A total of 633 patients underwent rectal anastomosis ( anastomotic leakage = 40 ; 6.3 percent ) : 30-day mortality : 10 percent in the leak group , and 2 percent in the nonleak group ( P = 0.014 ) ; cumulative five-year estimate of local recurrence : 25.1 ( 95 percent confidence interval , 9.6–40.5 ) percent in the leak group , and 10.4 ( 95 percent confidence interval , 7.7–13 ) percent in the nonleak group ( P = 0.007 ) . Cumulative five-year estimate of overall survival : 52.8 ( 95 percent confidence interval , 36.1–69.4 ) percent in the leak group , and 63.9 ( 95 percent confidence interval , 59.9–67.9 ) percent in the nonleak group ( P = 0.19 ) . CONCLUSIONS After rectal anastomosis , an anastomotic leak is associated with a significant increase in local recurrence The role of laparoscopic surgery in the management of cancer of the rectum remains controversial . The main concern is the risk of port-site metastasis and neoplastic dissemination . The aim of this study was to evaluate prospect ively 29 patients who underwent laparoscopic resection with total mesorectum excision for lower rectal carcinoma with a mean follow-up of 7 years . From January 1993 to December 1998 , 29 patients with proven low ( < 10 cm from the anal verge ) rectal cancer were operated by a laparoscopic approach . They were followed up at 1- , 3- , and then every 6-month intervals , postoperatively for an average of 7 years . Mean operative time was 157 ± 46 minutes . The conversion rate was 13.7 % ( 4 cases ) : 1 for tumor invasion of adjacent structures , 2 for inadequate margins of resection , and 1 for locally advanced cancer . First flatus occurred after 37.3 ± 11.5 hours , and oral feeding started at 48.3 ± 23 hours postoperatively . The length of the suprapubic incision for extraction of the specimen was 5.6 ± 1.7 cm . Hospital stay was 7.2 ± 3.0 days . There were no deaths . The morbidity rate was 14.8 % . Length of the specimen , lateral and distal margins , and the number of lymph nodes resected were comparable to those of an open surgical approach . The average postoperative follow-up was 7 years ( 5 - 10 years ) . The late complication rate was 3.7 % . There were no port-site metastases . Five-year recurrence rates were 0 % , 22 % , and 37 % for Duke 's A , B , and C cancers , respectively . The 5-year survival rate was 100 % for Duke 's A , 89 % for B , and 50 % for C. Laparoscopic resection for low rectal cancer with total mesorectum excision can be performed with the same oncologic principles , low morbidity , and long-term complications . Five-year survival and recurrence rates are comparable to those of open surgery BACKGROUND The aim of this study was to evaluate whether the use of fibrin glue as a sealant over an anastomosis is a risk factor for anastomotic leakage after laparoscopic rectal cancer surgery . METHODS Prospect i ve data were collected from 223 patients with rectal cancer who underwent laparoscopic resection without defunctioning stoma . RESULTS A total of 104 patients underwent laparoscopic rectal resection , followed by the application of fibrin glue over the stapled anastomosis , while 119 underwent surgery alone . No difference in clinical ly significant leakage was observed between the fibrin and the nonfibrin groups ( 5.8 % vs 10.9 % , P = .169 ) . In multivariate analysis , extraperitoneal tumor location and operation duration > 220 minutes were independently associated with anastomotic leakage . CONCLUSIONS Significant predictors of anastomotic leakage include extraperitoneal tumor location and operation length > 220 minutes . Fibrin glue application over the stapled anastomosis was not found to be significantly associated with anastomotic leakage |
495 | 23,903,965 | No differential effects in terms of route of administration , time of commencing therapy and dose of progesterone were observed for the majority of outcomes examined .
The use of progesterone is associated with benefits in infant health following administration in women considered to be at increased risk of preterm birth due either to a prior preterm birth or where a short cervix has been identified on ultrasound examination . | BACKGROUND Preterm birth is a major complication of pregnancy associated with perinatal mortality and morbidity .
Progesterone for the prevention of preterm labour has been advocated .
OBJECTIVES To assess the benefits and harms of progesterone for the prevention of preterm birth for women considered to be at increased risk of preterm birth and their infants . | We compared neonatal outcomes in twin pregnancies following moderately preterm birth ( MPTB ) , late preterm birth ( LPTB ) , and term birth . A secondary analysis of a multicenter , r and omized controlled trial of multiple gestations was conducted . MPTB was defined as delivery between 32 (0)/(7 ) and 33 (6)/(7 ) weeks and LPTB between 34 (0)/(7 ) and 36 (6)/(7 ) weeks . Primary outcome was a neonatal outcome composite consisting of one or more of the following : neonatal death , respiratory distress syndrome , early onset culture-proven sepsis , stage 2 or 3 necrotizing enterocolitis , bronchopulmonary dysplasia , grade 3 or 4 intraventricular hemorrhage , periventricular leukomalacia , pneumonia , or severe retinopathy of prematurity . Among 552 twin pregnancies , the MPTB rate was 14.5 % , LPTB 49.8 % , and term birth rate 35.7 % . The rate of the primary outcome was different between groups : 30.0 % for MPTB , 12.8 % for LPTB , 0.5 % for term birth ( P < 0.001 ) . Compared with term neonates , the primary neonatal outcome composite was increased following MPTB ( relative risk [ RR ] 58.5 ; 95 % confidence interval [ CI ] 11.3 to 1693.0 ) and LPTB ( RR 24.9 ; 95 % CI 4.8 to 732.2 ) . Twin pregnancies born moderately and late preterm encounter higher rates of neonatal morbidities compared with twins born at term OBJECTIVES To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth . METHODS We performed a planned secondary analysis from a large , multinational preterm birth prevention trial of daily intravaginal progesterone gel , 90 mg , compared with placebo in women with a history of spontaneous preterm birth or premature cervical shortening . Transvaginal cervical length measurements were obtained in all r and omized patients at baseline ( 18 + 0 to 22 + 6 weeks ' gestation ) and at 28 weeks ' gestation . For this secondary analysis , the difference in cervical length between these time points was compared for the study population with a history of spontaneous preterm birth and for a population with premature cervical shortening ( < or = 30 mm ) at r and omization . Differences between groups in cervical length for the 28-week examination were analyzed using ANCOVA , including adjustment for relevant clinical parameters and maternal characteristics . RESULTS Data were analyzed from 547 r and omized patients with a history of preterm birth . The progesterone-treated patients had significantly less cervical shortening than the placebo group ( difference 1.6 ( 95 % CI , 0.3 - 3.0 ) mm ; P = 0.02 , ANCOVA ) . In the population of 104 subjects with premature cervical shortening at r and omization , the cervical length also differed significantly on multivariable analysis , with the treatment group preserving more cervical length than the placebo group ( difference 3.3 ( 95 % CI , 0.3 - 6.2 ) mm ; P = 0.03 , ANCOVA ) , with adjustment for differences in cervical length at screening . A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to < or = 25 mm and a > or = 50 % reduction in cervical length from baseline in this sub population . CONCLUSIONS Intravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth BACKGROUND Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss . AIM To test the hypothesis that progesterone prophylaxis may reduce this . STUDY DESIGN A r and omised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls . RESULTS There were no differences in frequency of miscarriage , preterm delivery or neonatal outcome . CONCLUSION Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome 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 : Background 15 % of multiple pregnancies ends in a preterm delivery , which can lead to mortality and severe long term neonatal morbidity . At present , no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists . Prophylactic administration of 17-alpha hydroxyprogesterone caproate ( 17OHPC ) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery . At present , there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies . Methods / Design We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies . Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled , double blinded r and omised study comparing weekly 250 mg 17OHPC intramuscular injections from 16–20 weeks up to 36 weeks of gestation versus placebo . At study entry , cervical length will be measured . The primary outcome is composite bad neonatal condition ( perinatal death or severe morbidity ) . Secondary outcome measures are time to delivery , preterm birth rate before 32 and 37 weeks , days of admission in neonatal intensive care unit , maternal morbidity , maternal admission days for preterm labour and costs . We need to include 660 women to indicate a reduction in bad neonatal outcome from 15 % to 8 % . Analysis will be by intention to treat . We will also analyse whether the treatment effect is dependent on cervical length . Discussion This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies . Trial registration Current Controlled Trials IS RCT Objective . To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16–20 weeks in women with twin gestations who received 17-α hydroxyprogesterone caproate ( 17OHPC ) or placebo . Methods . This is a secondary analysis of a r and omised , double-blind , placebo-controlled trial of twin gestations exposed to 17OHPC or placebo . Baseline transvaginal ultrasound evaluation of cervical length was performed prior to treatment assignment at 16–20 weeks . Cervical length measurements were categorised according to the 10th , 25th , 50th and 75th percentiles in the women studied . The effect of 17OHPC administration in women with a short ( 25th percentile ) and long ( 75th percentile ) cervix was evaluated . Results . Of 661 twin gestations studied , 221 ( 33.4 % ) women enrolled at 11 centers underwent cervical length measurement . The 10th , 25th , 50th , 75th percentiles for cervical length at 16–20 weeks were 32 , 36 , 40 and 44 mm , respectively . The risk of preterm birth < 35 weeks was increased in women with a cervical length < 25th percentile ( 55.8 vs. 36.9 % , p = 0.02 ) . However , a cervical length > 75th percentile at this gestational age interval was not protective for preterm birth ( 36.5 vs. 42.9 % , p = 0.42 ) . Administration of 17OHPC did not reduce preterm birth before 35 weeks among those with either a short or a long cervix ( 64.3 vs. 45.8 % , p = 0.18 and 38.1 vs. 35.5 % , p = 0.85 , respectively ) . Conclusion . Women with twin gestations and a cervical length below the 25th percentile at 16–20 weeks had higher rates of preterm birth . In this subgroup of women , 17 OHPC did not prevent preterm birth before 35 weeks gestation . A cervical length above the 75th percentile at 16–20 weeks did not significantly reduce the risk of preterm birth in this high risk population 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 The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection ( ICSI ) pregnancies . A single-centre prospect i ve placebo-controlled r and omized study was performed . A total of 313 IVF/ICSI pregnant patients were r and omized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo , starting from mid-trimester up to 37 weeks or delivery . Amongst the patients , there were 215 singleton and 91 twin pregnancies . There was no significant difference in risk of preterm birth among all patients ( OR 0.672 , 95 % CI 0.42 - 1.0 . There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm ( OR 0.53 , 95 % CI 0.28 - 0.97 ) and no significant difference between both arms in twin pregnancies ( OR 0.735 , 95 % CI 0.36 - 2 ) . In conclusion , the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton , but not in twin , IVF/ICSI pregnancies Background Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity . Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity . Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix . However , it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women . Methods / Design We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth . In these women , we will measure cervical length at the st and ard anomaly scan performed between 18 and 22 weeks . Women with cervical length ≤ 30 mm at two independent measurements will be r and omly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks . The primary outcome of this trial is adverse neonatal condition , defined as a composite outcome of neonatal mortality and severe morbidity . Secondary outcomes are time to delivery , preterm birth rate before 32 , 34 and 37 weeks , days of admission in neonatal intensive care unit , maternal morbidity , maternal admission days for preterm labour and costs . We will assess growth , physical condition and neurodevelopmental outcome of the children at two years of age . Discussion This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18 - 22 weeks and subsequent progesterone treatment among low risk women . Trial registration Netherl and s Trial Register ( NTR ) : 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 OBJECTIVES Preterm birth contributes to a range of healthcare problems amongst infants surmounting to sizeable healthcare costs . Twin pregnancies are at particular risk of preterm birth . The objective of this study was to assess the cost-effectiveness of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies . METHODS An economic evaluation was conducted alongside a r and omized placebo controlled trial ( the STOPPIT trial ) of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies . Five hundred women were recruited from nine maternity hospitals in the United Kingdom . The outcomes of the economic evaluation were presented in terms of net benefit statistics , cost-effectiveness acceptability curves , generated using the nonparametric bootstrap method , and the expected value of perfect information . RESULTS Mean health service costs between the period of r and omization and discharge for mother and infant were 28,031 pound sterling in the progesterone group and 25,972 pound sterling in the placebo group , generating a mean nonsignificant cost difference of 2,059 pound sterling ( bootstrap mean cost difference 2,334 pound sterling ; 95 percent confidence interval : -5,023 pound sterling , 9,142 pound sterling ; p = .33 ) . The probability of progesterone being cost-effective was 20 percent at a willingness to pay threshold of 30,000 pound sterling per preterm birth prevented . There is little economic justification for conducting further research into the use of vaginal progesterone gel in twin pregnancies for the prevention of preterm birth . CONCLUSIONS Further studies of preventive interventions for preterm birth more generally are required given the scale of the clinical and economic burden of this condition . These studies should be sufficiently powered for economic endpoints and extend beyond hospital discharge Background Preterm birth is a global problem , with a prevalence of 8 to 12 % depending on location . Several large trials and systematic review s have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy ( including those with a short cervix or previous preterm birth ) . Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses . Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child , despite those in the “ progesterone ” group having a lower incidence of preterm birth . Methods / Design The OPPTIMUM study is a double blind r and omized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit . Specifically it will study whether , in women with singleton pregnancy and at high risk of preterm labour , prophylactic vaginal natural progesterone , 200 mg daily from 22 – 34 weeks gestation , compared to placebo , improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery ( before 34 weeks ) , improves neonatal outcome by reducing a composite of death and major morbidity , and leads to improved childhood cognitive and neurosensory outcomes at two years of age . Recruitment began in 2009 and is scheduled to close in Spring 2013 . As of May 2012 , over 800 women had been r and omized in 60 sites . Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth . Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome .Trial registration IS RCT Background Neonatal respiratory distress syndrome , as a consequence of preterm birth , is a major cause of early mortality and morbidity during infancy and childhood . Survivors of preterm birth continue to remain at considerable risk of both chronic lung disease and long-term neurological h and icap . Progesterone is involved in the maintenance of uterine quiescence through modulation of the calcium-calmodulin-myosin-light-chain-kinase system in smooth muscle cells . The withdrawal of progesterone , either actual or functional is thought to be an antecedent to the onset of labour . While there have been recent reports of progesterone supplementation for women at risk of preterm birth which show promise in this intervention , there is currently insufficient data on clinical ly important outcomes for both women and infants to enable informed clinical decision-making . The aims of this r and omised , double blind , placebo controlled trial are to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth will reduce the risk and severity of respiratory distress syndrome , so improving their infant 's health , without increasing maternal risks . Methods Design : Multicentred r and omised , double blind , placebo-controlled trial . Inclusion Criteria : pregnant women with a live fetus , and a history of prior preterm birth at less than 37 weeks gestation and greater than 20 weeks gestation in the immediately preceding pregnancy , where onset of labour occurred spontaneously , or in association with cervical incompetence , or following preterm prelabour ruptured membranes . Trial Entry & R and omisation : After obtaining written informed consent , eligible women will be r and omised between 18 and 23 + 6 weeks gestation using a central telephone r and omisation service . The r and omisation schedule prepared by non clinical research staff will use balanced variable blocks , with stratification according to plurality of the pregnancy and centre where planned to give birth . Eligible women will be r and omised to either vaginal progesterone or vaginal placebo . Study Medication & Treatment Schedules : Treatment packs will appear identical . Woman , caregivers and research staff will be blinded to treatment allocation . Primary Study Outcome : Neonatal Respiratory Distress Syndrome ( defined by incidence and severity ) . Sample Size : of 984 women to show a 40 % reduction in respiratory distress syndrome from 15 % to 9 % ( p = 0.05 , 80 % power ) . Discussion This is a protocol for a r and omised trial . Clinical Trial Registration Current Controlled Trials IS RCT OBJECTIVE To test whether 17 alpha-hydroxyprogesterone caproate ( 17P ) will reduce neonatal morbidity by increasing gestational age at delivery in triplet pregnancies . STUDY DESIGN Double-blind , r and omized clinical trial . Mothers carrying trichorionic-triamniotic triplets were r and omly assigned ( in a 2:1 ratio ) to weekly injections of 250 mg of 17P or placebo , starting at 16 - 22 weeks and continued until 34 weeks . Primary outcome was composite neonatal morbidity . RESULTS Fifty-six women were r and omized to 17P and 25 to placebo . Composite neonatal morbidity occurred with similar frequency in the 17P and placebo groups ( 38 % vs 41 % , respectively ; P = .71 ) . Mean gestational age at delivery was not affected by 17P ( 31.9 vs 31.8 weeks ; P = .36 ) . There were 13 midtrimester fetal losses with 17P vs none with placebo ( P < .02 ) . CONCLUSION In triplet pregnancy , prophylactic treatment with 17P did not reduce neonatal morbidity or prolong gestation but was associated with increased midtrimester fetal loss 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 OBJECTIVE To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester . METHODS This was a planned , but modified , secondary analysis of our multinational , multicenter , r and omized , placebo-controlled trial , in which women were r and omized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo . Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation . Treatment continued until either delivery , 37 weeks of gestation or development of preterm rupture of membranes . Maternal and neonatal outcomes were evaluated for the subset of all r and omized women with cervical length < 28 mm at enrollment . The primary outcome was preterm birth at < /= 32 weeks . RESULTS A cervical length < 28 mm was identified in 46 r and omized women : 19 of 313 who received progesterone and 27 of 307 who received the placebo . Baseline characteristics of the two groups were similar . In women with a cervical length < 28 mm , the rate of preterm birth at < /= 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo ( 0 % vs. 29.6 % , P = 0.014 ) . With progesterone , there were fewer admissions into the neonatal intensive care unit ( NICU ; 15.8 % vs. 51.9 % , P = 0.016 ) and shorter NICU stays ( 1.1 vs. 16.5 days , P = 0.013 ) . There was also a trend toward a decreased rate of neonatal respiratory distress syndrome ( 5.3 % vs. 29.6 % , P = 0.060 ) . CONCLUSION Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length Background Progestational agents may reduce the risk of preterm birth in women with various risk factors . We sought to test the hypothesis that a weekly dose of 17-hydroxyprogesterone caproate ( 17P ) given to women with preterm rupture of the membranes ( PROM ) will prolong pregnancy and thereby reduce neonatal morbidity . Methods Double-blind , placebo-controlled r and omized clinical trial . Women with PROM at 23.0 to 31.9 weeks of gestation were r and omly assigned to receive a weekly intramuscular injection of 17P ( 250 mg in 1 mL castor oil ) or placebo ( 1 mL castor oil ) . The primary outcome was the rate of continuing the pregnancy until 34.0 weeks of gestation or until documentation of fetal lung maturity at 32.0 to 33.9 weeks of gestation . Planned secondary outcomes were duration of latency period and rate of composite neonatal morbidity . Enrollment of 111 participants per group , 222 total , was planned to yield 80 % power to detect an increase in the primary outcome from 30 % with placebo to 50 % with 17P . Results Twelve women were enrolled of whom 4 were r and omly assigned to receive 17P and 8 to receive placebo . The trial was terminated prematurely because of two separate issues related to the supply of 17P . No adverse events attributable to 17P were identified . Conclusion Because of premature termination , the trial does not have adequate statistical power to evaluate efficacy or safety of 17P in women with PROM . Nonetheless , ethical principles dictate that we report the results , which may contribute to possible future metaanalyses and systematic review s . Trial Registration Clinical Trials.gov : NCT01119963Supported by a research grant from the Center for Research , Education , and Quality , Pediatrix Medical Group , Sunrise , BACKGROUND Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies . The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate ( 17P ) may reduce the risk of preterm delivery . METHODS We conducted a double-blind , placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery . Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and r and omly assigned by a central data center , in a 2:1 ratio , to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo ; injections were continued until delivery or to 36 weeks of gestation . The primary outcome was preterm delivery before 37 weeks of gestation . Analysis was performed according to the intention-to-treat principle . RESULTS Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar . Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation ( incidence , 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group ; relative risk , 0.66 [ 95 percent confidence interval , 0.54 to 0.81 ] ) , delivery at less than 35 weeks of gestation ( incidence , 20.6 percent vs. 30.7 percent ; relative risk , 0.67 [ 95 percent confidence interval , 0.48 to 0.93 ] ) , and delivery at less than 32 weeks of gestation ( 11.4 percent vs. 19.6 percent ; relative risk , 0.58 [ 95 percent confidence interval , 0.37 to 0.91 ] ) . Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis , intraventricular hemorrhage , and need for supplemental oxygen . CONCLUSIONS Weekly injections of 17P result ed in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants Objective To compare the effects of four methods of analysis on the results of r and omised controlled trials that recruit women with multiple pregnancies and measure outcomes on their babies Objective : To compare preterm birth rate and neonatal outcome in twin gestations r and omized to either 17 alpha-hydroxyprogesterone caproate ( 17P ) or placebo . Material s and Methods : Women with twin gestations between 20–30 weeks were r and omized to receive weekly injections of either 250 mg 17P injection ( Group I ) , or placebo ( Group II ) . Maternal and neonatal outcome data was recorded . Results : Thirty twin intrauterine pregnancies were r and omized ; 16 received 17P and 14 received placebo . Demographic data as well as past history and gestational age at r and omization were equivalent between groups ( P = 0.286–0.847 ) . All patients in both groups were Medicaid recipients . The incidence of preterm labor ( P = 0.980 ) , and premature rupture of the membranes ( P = 0.525 ) were the same between groups . Gestational age at delivery was also similar between 17P ( 33.9 weeks ) versus placebo ( 33.1 weeks , P = 0.190 ) as was the incidence of preterm birth < 35 weeks ( 44 % vs 79 % , P = 0.117 ) . Infant weight ( P = 0.641 ) , Apgar score at 5 minutes ( P = 0.338 ) as well as neonatal morbidity such as respiratory distress syndrome ( P = 0.838 ) , patent ductus arteriosus ( P = 0.704 ) , intraventricular hemorrhage ( P = 0.851 ) and necrotizing enterocolitis ( P = 0.946 ) showed no difference . Days spent in the NICU among 17P ( 18.4 ) versus placebo ( 17.3 , P = 0.155 ) , neonatal death ( P = 0.359 ) and those infants discharged with neurologic h and icap ( P = 0.594 ) were not different between groups . Conclusion : Amongst this group of twin gestations weekly 17HP injections did not reduce the incidence of preterm birth or the complications associated with prematurity OBJECTIVE The objectives of the study was to determine whether salivary progesterone ( P ) or estriol ( E3 ) concentration at 16 - 20 weeks ' gestation predicts preterm birth or the response to 17alpha-hydroxyprogesterone caproate ( 17OHPC ) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed . STUDY DESIGN This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth . Baseline saliva was assayed for P and E3 . Weekly salivary sample s were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter r and omized trial of 17OHPC to prevent recurrent preterm delivery . RESULTS Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth . However , 17OHPC prevented preterm birth comparably , regardless of baseline salivary hormone concentrations . 17OHPC did not alter the trajectory of salivary P over pregnancy , but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio . CONCLUSION 17OHPC flattened the trajectory of E3 in the second half of pregnancy , suggesting that the drug influences the fetoplacental unit OBJECTIVE The purpose of this study was to examine the utility of a single second-trimester plasma corticotropin-releasing hormone measurement as a marker for preterm delivery in women at high risk for preterm delivery . STUDY DESIGN This is an analysis of data from a multicenter placebo-controlled trial design ed to evaluate the role of 17 alpha hydroxyprogesterone caproate ( 17P ) in the prevention of recurrent preterm birth . Women with a documented history of a previous spontaneous preterm birth at < 37 weeks were enrolled ( 16 - 20 wks ) and r and omly assigned in a 2 to 1 ratio to weekly injections of 17P or matching placebo . Blood was collected before treatment in 170 patients ( 113 assigned 17P and 57 placebo ) who were enrolled at 11 of the 19 centers . Plasma levels of corticotropin-releasing hormone were compared between those who delivered preterm and those delivering at term . Data were analyzed using the Wilcoxon rank-sum test . RESULTS The overall rates of preterm birth in this cohort of 170 patients were 35.9 % at < 37 weeks ( 31.9 % progesterone , 43.9 % placebo ) , and 19.4 % at < 35 weeks ( 18.6 % vs 21.1 % ) . The median levels of corticotropin-releasing hormone were similar between those delivering at < 37 weeks and those delivering > or = 37 weeks ( 0.39 ng/mL vs 0.37 ng/mL , P = .08 ) . In addition , there were no differences in corticotropin-releasing hormone levels among those who delivered at < 35 weeks or > or = 35 weeks ( 0.36 vs 0.38 , P = .90 ) . Moreover , there were no differences in corticotropin-releasing hormone levels among those in the placebo group who delivered at < 37 or > or = 37 weeks ( 0.40 vs 0.41 , P = .72 ) and at < 35 or > or = 35 weeks ( P = .64 ) . CONCLUSION A single measurement of corticotropin-releasing hormone at 16 to 20 weeks ' gestation is not a good biomarker for recurrent preterm delivery in patients at high risk for this complication 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 OBJECTIVE The primary objective of this prospect i ve study was to test whether preterm birth prevention education plus increased clinic visits and selected prophylactic interventions reduce preterm birth . STUDY DESIGN Eight West Los Angeles prenatal county clinics , comparable with respect to selected demographics , were r and omized to be either experimental or control clinics . High-risk patients in all clinics were identified with a risk scoring system derived from a similar population . High-risk patients ( N = 1774 ) in experimental clinics were offered a program of education and more frequent visits and were r and omized to receive various secondary intervention protocol s in addition to the basic interventions of education and more frequent visits . Control clinic patients ( N = 880 ) received st and ard county care . RESULTS Preterm birth rates were 19 % lower among the experimental high-risk patients ( 7.4 % vs 9.1 % ) , and differences were significant ( p < 0.05 ) when preterm risk was taken into account . There was no evidence to suggest that the secondary interventions provided added benefit over the primary intervention protocol of preterm birth prevention education and increased visits . CONCLUSION The 19 % reduction in preterm birth rate observed in the experimental clinics suggest an overall program benefit from a protocol that offered education , more frequent visits , and greater attention given to patients while the selected interventions were applied Objective : To examine how demographic and pregnancy characteristics can affect the risk of recurrent preterm delivery and the how the effectiveness of progesterone treatment for prevention alters these relationships . Methods : This was a secondary analysis of a r and omized trial of 17α-hydroxyprogesterone caproate to prevent recurrent preterm delivery in women at risk . Associations of risk factors for preterm delivery ( less than 37 completed weeks of gestation ) were examined separately for the women in the 17α-hydroxyprogesterone caproate ( n = 310 ) and placebo ( n = 153 ) groups . Results : Univariate analysis found that the number of previous preterm deliveries and whether the penultimate delivery was preterm were significant risk factors for preterm delivery in both the placebo and progesterone groups . High body mass index was protective of preterm birth in the placebo group . Multivariate analysis found progesterone treatment to cancel the risk of more than 1 previous preterm delivery , but not the risk associated with the penultimate pregnancy delivered preterm . Obesity was associated with lower risk for preterm delivery in the placebo group but not in the women treated with progesterone . Conclusion : The use of 17α-hydroxyprogesterone caproate in women with a previous preterm delivery reduces the overall risk of preterm delivery and changes the epidemiology of risk factors for recurrent preterm delivery . In particular , these data suggest that 17α-hydroxyprogesterone caproate reduces the risk of a history of more than 1 preterm delivery . Level of Evidence : OBJECTIVE : To estimate whether administration of 17&agr;-hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate . METHODS : We conducted a multicenter , double-blind , placebo-controlled r and omized trial in 55 obstetric clinics in the Netherl and s. Women with a multiple pregnancy were r and omized to weekly injections of either 250 mg 17&agr;-hydroxyprogesterone caproate or placebo , starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation . The main outcome measure was adverse neonatal outcome . Secondary outcome measures were gestational age at delivery and delivery before 28 , 32 , and 37 weeks of gestation . RESULTS : We r and omized 671 women . A composite measure of adverse neonatal outcome was present in 110 children ( 16 % ) born to mothers in the 17&agr;-hydroxyprogesterone caproate group , and in 80 children ( 12 % ) of mothers in the placebo group ( relative risk [ RR ] 1.34 ; 95 % confidence interval [ CI ] 0.95–1.89 ) . The mean gestational age at delivery was 35.4 weeks for the 17&agr;-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group ( P=.32 ) . Treatment with 17&agr;-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks ( 6 % in the 17&agr;-hydroxyprogesterone caproate group compared with 5 % in the placebo group , RR 1.04 ; 95 % CI 0.56–1.94 ) , 32 weeks ( 14 % compared with 10 % , RR 1.37 ; 95 % CI 0.91–2.05 ) , or 37 weeks of gestation ( 55 % compared with 50 % , RR 1.11 ; 95 % CI 0.97–1.28 ) . CONCLUSION : 17&agr;-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies . CLINICAL TRIAL REGISTRATION : IS RCT N Register , www.is rct n.org , IS RCT N40512715 . LEVEL OF EVIDENCE : OBJECTIVE The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate ( 17P ) to reduce preterm delivery . STUDY DESIGN This open-label , multicenter , r and omized controlled trial included women with singleton pregnancies admitted at 24 - 31 weeks ' gestation and cervical length less than 25 mm for preterm labor successfully arrested by tocolytic treatment . R and omization assigned them to receive ( or not ) 500 mg of intramuscular 17P after tocolysis ended , repeated semiweekly until 36 weeks or preterm delivery . The primary outcome was the time from r and omization to delivery . RESULTS Outcome data were available for 184 of 188 women r and omized . The 17P and control groups ( similar for most baseline characteristics ) did not differ significantly for median [ interquartile range ] time to delivery ( 64 [ 42 - 79 ] and 67 [ 46 - 83 ] days , respectively ) or rates of delivery before 37 , 34 , or 32 weeks of gestation or adverse perinatal outcomes . CONCLUSION Semiweekly injections of 17P did not prolong pregnancy significantly in women with tocolysis-arrested preterm labor OBJECTIVE Studies on high-risk singleton gestations have shown a preventive effect of progesterone treatment on preterm delivery . This study was conducted to investigate the preventive effect of vaginal micronized progesterone in a large population of twin gestations . METHODS This was a double-blind , placebo-controlled r and omized trial performed in 17 centers in Denmark and Austria . Women with twin gestations were r and omized to daily treatment with progesterone pessaries or apparently identical placebo pessaries , starting from 20 - 24 weeks until 34 weeks ' gestation . Primary outcome was incidence of delivery before 34 weeks ' gestation . Secondary outcomes were maternal and neonatal complications and long-term infant follow-up , by Ages and Stages Question naire ( ASQ ) , 6 months and 18 months after the expected date of delivery . We also up date d a published meta- analysis to include our data and those of another recently published twin trial . RESULTS A total of 677 women were r and omized to the two treatments . Two women in the placebo group were lost to follow-up . Baseline characteristics for the groups were similar . Incidence of delivery before 34 weeks was 15.3 % in the progesterone group vs 18.5 % in the placebo group ( odds ratio , 0.8 ( 95 % CI , 0.5 - 1.2 ) ) . Risks of maternal and neonatal complications were comparable for the two groups . Mean ASQ scores at 6 months and 18 months were not significantly different between the two groups ( 215 for infants in the progesterone group and 218 for infants in the placebo group at 6 months ( P = 0.45 ) and 193 and 194 , respectively , at 18 months ( P = 0.89 ) ) . The meta- analysis gave a pooled odds ratio of 1.06 ( 95 % CI , 0.86 - 1.31 ) . CONCLUSION Progesterone treatment did not prevent preterm delivery in twin gestations . There were no harmful effects to fetuses and infants of maternal progesterone treatment 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 ] . ) 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 To compare the rates of gestational diabetes among women who received serial doses of 17-alpha hydroxyprogesterone caproate vs placebo . STUDY DESIGN Secondary analysis of 2 double-blind r and omized placebo-controlled trials of 17-alpha hydroxyprogesterone caproate given to women at risk for preterm delivery . The incidence of gestational diabetes was compared between women who received 17-alpha hydroxyprogesterone caproate or placebo . RESULTS We included 1094 women ; 441 had singleton and 653 had twin gestations . Combining the 2 studies , 616 received 17-alpha hydroxyprogesterone caproate and 478 received placebo . Among singleton and twin pregnancies , rates of gestational diabetes were similar in women receiving 17-alpha hydroxyprogesterone caproate vs placebo ( 5.8 % vs 4.7 % ; P = .64 and 7.4 % vs 7.6 % ; P = .94 , respectively ) . In the multivariable model , progesterone was not associated with gestational diabetes ( adjusted odds ratio , 1.04 ; 95 % confidence interval , 0.62 - 1.73 ) . CONCLUSION Weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of gestational diabetes in either singleton or twin pregnancies 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 OBJECTIVE : To assess whether 17 alpha-hydroxyprogesterone caproate reduces the rate of preterm birth in women carrying triplets . METHODS : We performed this r and omized , double-blinded , placebo-controlled trial in 14 centers . Healthy women with triplets were r and omly assigned to weekly intramuscular injections of either 250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo , starting at 16–20 weeks and ending at delivery or 35 weeks of gestation . The primary study outcome was delivery or fetal loss before 35 weeks . RESULTS : One hundred thirty-four women were assigned , 71 to 17 alpha-hydroxyprogesterone caproate and 63 to placebo ; none were lost to follow-up . Baseline demographic data were similar in the two groups . The proportion of women experiencing the primary outcome ( a composite of delivery or fetal loss before 35 0/7 weeks ) was similar in the two treatment groups : 83 % of pregnancies in the 17 alpha-hydroxyprogesterone caproate group and 84 % in the placebo group , relative risk 1.0 , 95 % confidence interval 0.9–1.1 . The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident regardless of the conception method or whether a gestational age cutoff for delivery was set at 32 or 28 weeks . CONCLUSION : Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with triplet gestations . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00099164 LEVEL OF EVIDENCE : 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 Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90–200 mg of daily vaginal natural progesterone . Higher doses have not been tested . Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone ( 200 and 400 mg ) , compared with placebo , for preventing preterm birth in unselected twin pregnancies Objective . A planned study to test the hypothesis that dydrogesterone given during the first trimester of pregnancy can positively influence the immune system of women suffering from recurrent miscarriages and thereby lead to successful pregnancies . The primary objective is to show whether the administration of dydrogesterone during the first trimester of pregnancy increases the release of progesterone-induced blocking factor ( PIBF ) and causes a shift from Th-1 cytokines to Th-2 cytokines . Further objectives are an analysis of pregnancy outcome and to investigate the tolerability and safety of dydrogesterone use during pregnancy . Methods . A prospect ively r and omized , placebo-controlled study of 20 mg dydrogesterone per day during the first trimester of pregnancy in women aged between 18 and 38 and with a history of idiopathic recurrent miscarriage . Start of treatment will be after ovulation . The study will be conducted in a two-stage adaptive design , starting with a sample size of 20 patients per treatment group . The concentrations of Th-1 and Th-2 cytokines in the serum and PIBF in the urine will be measured . Efficacy will be measured primarily by the ratio IFNγ/IL-10 . Conclusion . The results of this study will contribute to the discussion of a current concept of immunomodulation in pregnancy and potentially provide a treatment option for patients suffering from recurrent miscarriage 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 OBJECTIVE We sought to determine if 17-alpha-hydroxyprogesterone ( 17P ) extends gestation vs placebo in women with preterm premature rupture of the membranes ( PPROM ) . STUDY DESIGN Women with vertex presentations with PPROM , 20 - 30 weeks ' gestation , were r and omized to receive weekly 17P or placebo in an attempt to prolong the pregnancy . A total of 69 patients ( 17P , n = 33 ; placebo , n = 36 ) were r and omized into this study . RESULTS Initial cervical dilatation , gestational age at enrollment , and interval to delivery were not different between the 2 groups ( P = .914 , .424 , and .146 , respectively ) . Time of r and omization to delivery ( P = .250 ) , mode of delivery ( relative risk , 1.16 ; 95 % confidence interval , 0.66 - 2.06 ) , and the neonatal outcome statistics of morbidity ( P = .820 ) and mortality ( relative risk , 1.28 ; 95 % confidence interval , 0.59 - 2.75 ) were similar between the 2 groups . CONCLUSION In patients with PPROM , 17P did not extend gestation vs placebo and can not be recommended for treatment in such women 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 OBJECTIVE We sought to determine whether prophylactic treatment with 17-alpha-hydroxyprogesterone caproate ( 17Pc ) in twin pregnancy will reduce neonatal morbidity ( primary outcome ) by prolonging pregnancy ( secondary outcome ) . STUDY DESIGN This was a double-blind , r and omized clinical trial . Mothers carrying dichorionic-diamniotic twins were r and omly assigned ( in a 2:1 ratio ) to weekly injections of 250 mg of 17Pc or placebo , starting at 16 - 24 weeks and continued until 34 weeks . RESULTS In all , 160 women were r and omized to 17Pc and 80 to placebo . Composite neonatal morbidity occurred with similar frequency in the 17Pc and placebo groups ( 14 % vs 12 % , respectively , P = .62 ) . Mean gestational age at delivery was not affected by 17Pc ( 35.3 vs 35.9 weeks , P = .10 ) , but a 3-day difference in median gestational age favored placebo ( P = .02 ) . There were no perinatal deaths with 17Pc and 3 with placebo . CONCLUSION In twin pregnancy , prophylactic treatment with 17Pc did not prolong gestation or reduce neonatal morbidity 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 OBJECTIVE We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome . STUDY DESIGN A total of 1711 multiparous women with singleton gestations were prospect ively evaluated at 23 to 24 weeks ' gestation . Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery . If a prior spontaneous preterm delivery had occurred , the gestation of the earliest prior delivery ( 13 - 22 , 23 - 27 , 28 - 34 , and 35 - 36 weeks ' gestation ) was recorded . Current gestations were categorized as spontaneous preterm delivery at < 28 , < 30 , < 32 , < 35 , or < 37 weeks ' gestation . The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence , gestational age , and cause of the earliest prior spontaneous preterm delivery . RESULTS The incidences of spontaneous preterm delivery before 28 , 30 , 32 , 35 , and 37 weeks ' gestation were 0.8 % , 1.1 % , 1.9 % , 5.1 % , and 11.9 % , respectively . Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery ( 21 . 7 % vs 8.8 % ; P < /=.001 ) . Gravid women with an early prior spontaneous preterm delivery ( 23 - 27 weeks ' gestation ) had a higher risk of recurrent spontaneous preterm delivery ( 27.1 % vs 8.8 % ; P < /=.001 ) . Prior spontaneous preterm delivery was more closely associated with subsequent early spontaneous preterm delivery at < 28 weeks ' gestation ( relative risk , 10.6 ) than for spontaneous preterm delivery overall ( relative risk , 2.5 ) . An early prior spontaneous preterm delivery ( 23 - 27 weeks ' gestation ) was most highly associated with early spontaneous preterm delivery ( < 28 weeks ' gestation ) in the current gestation ( relative risk , 22.1 ) . The relationship between prior spontaneous preterm delivery and current outcome was not as strong for those with a very early spontaneous preterm delivery ( 13 - 22 weeks ' gestation ) . Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and preterm labor was significantly associated with similar outcomes in the current gestation ( P < .001 ) . CONCLUSION Prior spontaneous preterm delivery is highly associated with recurrence in the current gestation . An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated with subsequent early spontaneous preterm delivery The effect of medroxyprogesterone acetate upon the duration and char acteristics of human gestation and labor was studied . 200 pregnant women ( 36 - 38 weeks gestation ) were r and omly assigned to a group receiving 20 mg 4 times/day or to a group receiving only the tablet base . This double-blind study failed to reveal any effect upon the duration of pregnancy or the characteristics of pregnancy labor or fetal conditions 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 OBJECTIVE Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality . 17-alpha hydroxyprogesterone caproate ( 17-OHP caproate ) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth ( sPTB ) . This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery . We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth ( 20 - 27.9 , 28 - 33.9 vs 34 - 36.9 weeks ) . STUDY DESIGN This was a secondary analysis of 459 women with a previous sPTB enrolled in a r and omized controlled trial evaluating 17-OHP caproate versus placebo . Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinical ly relevant groupings ( 20 - 27.9 , 28 - 33.9 , and 34 - 36.9 weeks ) . Statistical analysis included the chi-square , Fisher exact , and Kruskal-Wallis tests , logistic regression , and survival analysis using proportional hazards . RESULTS Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo ( P = .1 ) . Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo ( median 37.3 vs 35.4 weeks , P = .046 and 38.0 vs 36.7 weeks , P = .004 , respectively ) and were less likely to deliver < 37 weeks ( 42 % vs 63 % , P = .026 and 34 % vs 56 % , P = .005 , respectively ) . Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control . CONCLUSION 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall , and especially for women with a previous spontaneous PTB at < 34 weeks Aims : To assess the efficacy of vaginal micronized natural progesterone as a tocolytic and in maintenance therapy during threatened preterm birth . Methods : Eighty-three women with symptoms of threatened preterm birth were either r and omized to study groups receiving tocolytic treatment combined with intravaginal micronized natural progesterone ( 200 mg daily ) or to a control group receiving only tocolysis . Results : Micronized natural progesterone treatment result ed in a prolonged latency period of 32.1 ± 17.8 versus 21.2 ± 16.3 days in the control group and heavier birth weights of 2,982.8 ± 697.8 g versus 2,585.3 ± 746.6 g. No significant differences were found between the groups in admission to the neonatal intensive care unit , stay at the neonatal intensive care unit , need for a mechanical ventilator , respiratory distress syndrome or neonatal sepsis . Conclusion : The treatment of threatened preterm birth with tocolytics combined with intravaginal micronized natural progesterone significantly prolonged pregnancy and increased birth weight . However , an improvement in adverse perinatal outcomes was not observed 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 We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate ( 17P ) on cervical ripening is mediated by cervical proinflammatory agents . Women with singleton pregnancy and intact membranes , between 25 and 33 weeks + 6 days , were r and omly allocated either to observation ( 22 cases , controls ) or to receive 341 mg of intramuscular 17P ( 23 cases , 17P group ) , twice a week , until 36 weeks . Just before r and omization , 7 and 21 days later , a cervical swab for interleukin (IL)-1beta , IL-6 , IL-8 , tumor necrosis factor alpha ( TNF-alpha ) , and nitrates/nitrites ( NOx ) assays was collected . Moreover , an ultrasound measure of cervical length ( CL ) was performed at the same time . At r and omization , both groups of women showed similar levels of cervical ILs and NOx . In the 17P group , cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036 ) ; in controls , they remained stable throughout the observation period . There was no significant change in IL-6 , IL-8 , TNF-alpha , and NOx in either group . Women in the control group had a progressive CL shortening until day 21 ( median shortening of 4 mm ) , and this shortening was significantly less in the 17P group ( median shortening of 2 mm ; P = 0.017 ) . In patients at risk of preterm labor , high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix What is meant by intention-to-treat ? Why should data be analyzed in controlled trials in a way that all participants are included in the group to which they were r and omly assigned , regardless of whether they completed the intervention given to the group ? In this Tutorial , the logic of the intention-to-treat principle is outlined . It is shown that study results may be biased by excluding patients post hoc thus producing spurious effects that do not exist in the population under study . The intention-to-treat strategy avoids this bias |
496 | 30,322,815 | Conclusions : Published research of h and hygiene compliance measured by direct observation lacks validity . | HIGHLIGHTS Results of monitoring h and hygiene compliance by direct observation may be biased .
Background : H and hygiene is monitored by direct observation to improve practice , but this approach can potentially cause information , selection , and confounding bias , threatening the validity of findings .
The aim of this study was to identify and describe the potential biases in h and hygiene compliance monitoring by direct observation ; develop a typology of biases and propose improvements to reduce bias ; and increase the validity of compliance measurements . | Objective To determine the frequency and predictors of compliance with h and hygiene ( HH ) practice in pediatric intensive care . Design Observational , prospect i ve cohort study performed from February to April 2000 . Setting Three intensive care units at a tertiary care children ’s hospital . Participants Nurses , physicians , respiratory therapists , and other healthcare workers . Methods During 156 30-min daytime observation periods , an unidentified observer monitored 2811 opportunities for HH during patient care and recorded HH compliance . Measurements and Main Results Average HH compliance was 34 % ( 946/2811 ) . It was higher ( p < 0.001 ) among respiratory therapists ( 68 % ; 171/251 ) than physicians ( 37 % ; 157/426 ) or nurses ( 29 % ; 587/2031 ) . Contact with body fluid secretions was associated with the highest compliance ( 77 % ; 46/60 ) , and contact with wounds ( 71 % ; 10/14 ) or indwelling devices ( 66 % ; 110/167 ) were associated with somewhat lesser compliance . The following were important predictors of compliance ( all p < 0.01 ) : being a respiratory therapist ( odds ratio [ OR ] , 5.1 ) ; working in the neonatal intensive care unit ( OR , 1.6 ) ; and contact with invasive devices ( OR , 2.5 ) , wounds ( OR , 6.9 ) , or body fluids ( OR , 11.5 ) . Compliance was lowest after interrupted patient-care activities ( 9 % ; OR , 0.15 ) . Surprisingly , decreased patient-to-nurse ratio ( mean , 1.3 ± 0.3 ) or opportunities per hr of care ( mean , 37 ± 7 ) were not independent predictors of compliance . Conclusions Average HH compliance was low , but it increased during high-risk patient-care activities . Intensified efforts are necessary to increase caretakers ’ compliance and the awareness of the risk of bacterial contamination after interrupted patient-care activities Context : The role of h and hygiene in preventing health care associated infections ( HCAIs ) has been clearly established . However , compliance rates remain poor among health care personnel . Aims : a ) To investigate the health care workers ’ h and hygiene compliance rates in the intensive care unit ( ICU ) , b ) to assess reasons for non-compliance and c ) to study the efficacy of a multimodal intervention strategy at improving compliance . Setting s : A mixed medical – surgical ICU of a tertiary level hospital . Design : A before – after prospect i ve , observational , intervention study . Material s and Methods : All health care personnel who came in contact with patients in the ICU were observed for their h and hygiene compliance before and after a multimodal intervention strategy ( education , posters , verbal reminders and easy availability of products ) . A self-report question naire was also circulated to assess perceptions regarding compliance . Statistical analysis was done using χ2 test or Fisher exact test ( Epi info software ) . Results : H and hygiene compliance among medical personnel working in the ICU was 26 % and the most common reason cited for non-compliance was lack of time ( 37 % ) . The overall compliance improved significantly following the intervention to 57.36 % ( P<0.000 ) . All health care worker groups showed significant improvements : staff nurses ( 21.48–61.59 % , P<0.0000 ) , nursing students ( 9.86–33.33 % , P<0.0000 ) , resident trainees ( 21.62–60.71 % , P<0.0000 ) , visiting consultants ( 22–57.14 % , P=0.0001 ) , physiotherapists ( 70–75.95 % , P=0.413 ) and paramedical staff ( 10.71–55.45 % , P < 0.0000 ) . Conclusions : H and hygiene compliance among health care workers in the ICU is poor ; however , intervention strategies , such as the one used , can be useful in improving the compliance rates significantly Background Frequent h and washing can prevent infections , but non-compliance to h and hygiene is pervasive . Few theory- and evidence -based interventions to improve regular h and washing are available . Therefore , two intervention modules , a motivational and a self-regulatory one , were design ed and evaluated . Methods In a longitudinal study , 205 young adults , aged 18 to 26 years , were r and omized into two intervention groups . The Mot-SelfR group received first a motivational intervention ( Mot ; risk perception and outcome expectancies ) followed by a self-regulatory intervention ( SelfR ; perceived self-efficacy and planning ) 17 days later . The SelfR-Mot group received the same two intervention modules in the opposite order . Follow-up data were assessed 17 and 34 days after the baseline . Results Both intervention sequences led to an increase in h and washing frequency , intention , self-efficacy , and planning . Also , overall gains were found for the self-regulatory module ( increased planning and self-efficacy levels ) and the motivational module ( intention ) . Within groups , the self-regulatory module appeared to be more effective than the motivational module , independent of sequence . Conclusions Self-regulatory interventions can help individuals to exhibit more h and washing . Sequencing may be important as a motivation module ( Mot ) first helps to set the goal and a self-regulatory module ( SelfR ) then helps to translate this goal into actual behavior , but further research is needed to evaluate mechanisms BACKGROUND H and hygiene compliance among health care providers is considered to be the single most effective factor to reduce hospital acquired infections . Despite continuous education and awareness , compliance with h and hygiene guidelines has remained low , particularly during evening shifts . OBJECTIVE Our objective was to determine the compliance with h and hygiene guidelines among doctors , nurses , and paramedical staff during day and night duties in a multidisciplinary intensive care unit ( ICU ) . METHODS We used a prospect i ve , observational , 6-month study conducted in a 34-bed ICU within a tertiary care teaching hospital . All doctors , nurses , and paramedical staff in the ICU were included . An investigator , placed within the ICU setting , observed the h and hygiene practice s during day and night . Day and night shift change times were 08:00 and 20:00 hours , respectively . RESULTS Of the 5639 opportunities for h and hygiene , 3383 ( 59.9 % ) were properly performed . Overall rates of compliance were 66.1 % for doctors , 60.7 % for nurses , and 38.6 % for paramedical staff . H and hygiene compliance dropped during the night for doctors ( 81 % vs 46 % , respectively , P < .001 ) , for nurses ( 64 % vs 55 % , respectively , P = .02 ) , and for paramedical staff ( 44 % vs 31 % , respectively , P = .01 ) . Characterization of noncompliance is as follows : " No h and washing after procedure " in 41 % , " improper duration of h and washing " in 32 % , and " no h and washing done at all " in 27 % of the events . " No h and washing done at all " occurred in 55 % of the time at night with doctors having the highest rate of noncompliance , making 163 ( 34 % ) contacts without h and washing . CONCLUSION Whereas compliance with h and hygiene guidelines was lower at night compared with day , irrespective of discipline in all 3 groups of health care providers , both periods of compliance would benefit from additional training focusing on the importance of h and hygiene around the clock BACKGROUND Although h and hygiene ( HH ) compliance has been an important issue for years , the compliance rate is still a problem in health care today . METHODS This was an observational , prospect i ve , before- and -after study . We measured HH knowledge and HH compliance before ( baseline ) , directly after ( post strategy ) , and 6 months after the performance of HH team strategies ( follow-up ) . The study was composed of employed nurses and physicians working in the department of internal medicine of a university hospital . We performed a multifaceted improvement program including HH education , feedback , reminders , social influence activities including the use of role models , and improvement of HH facilities . RESULTS Ninety-two nurses and physicians were included . Compared with baseline , there was a significant improvement in the overall mean HH knowledge score at post strategy ( from 7.4 to 8.4 ) and follow-up ( from 7.4 to 8.3 ) . The overall HH compliance was 27 % at baseline , 83 % at post strategy , and 75 % at follow-up . At baseline , the compliance rate was 17 % in nurses and 43 % in physicians and significantly improved to 63 % in nurses and 91 % in physicians at follow-up . CONCLUSION Our multifaceted HH improvement program result ed in a sustained improvement of HH knowledge and compliance in nurses as well as physicians OBJECTIVES . H and hygiene promotion interventions rarely result in sustained improvement , and an assessment of their impact on individual infection risk has been lacking . We sought to measure the impact of h and hygiene promotion on health care worker compliance and health care – associated infection risk among neonates . METHODS . We conducted an intervention study with a 9-month follow-up among all of the health care workers at the neonatal unit of the Children 's Hospital , University of Geneva Hospitals , between March 2001 and February 2004 . A multifaceted h and hygiene education program was introduced with compliance assessed during successive observational surveys . Health care – associated infections were prospect ively monitored , and genotypic relatedness of bloodstream pathogens was assessed by pulsed-field gel electrophoresis . A comparison of observed h and hygiene compliance and infection rates before , during , and after the intervention was conducted . RESULTS . A total of 5325 opportunities for h and hygiene were observed . Overall compliance improved gradually from 42 % to 55 % across study phases . This trend remained significant after adjustment for possible confounders and paralleled the measured increase in h and -rub consumption ( from 66.6 to 89.2 L per 1000 patient-days ) . A 9-month follow-up survey showed sustained improvement in compliance ( 54 % ) , notably with direct patient contact ( 49 % at baseline vs 64 % at follow-up ) . Improved compliance was independently associated with infection risk reduction among very low birth weight neonates . Bacteremia caused by clonally related pathogens markedly decreased after the intervention . CONCLUSIONS . H and hygiene promotion , guided by health care workers ' perceptions , identification of the dynamics of bacterial contamination of health care workers ' h and s , and performance feedback , is effective in sustaining compliance improvement and is independently associated with infection risk reduction among high-risk neonates OBJECTIVES To assess h and washing frequency according to CDC recommendations ; and to test a simple intervention to increase h and washing compliance , design ed for the unique setting of the ED . METHODS A prospect i ve , observational , before- and -after study design with a convenience sampling technique was used to assess h and washing compliance in the ED of a 742-bed urban , university-affiliated medical center with 65,000 visits annually . Emergency physicians ( EPs ) , registered nurses ( RNs ) , and nurse practitioners ( NPs ) were informed that their patient encounters were being monitored , but the nature of the study was kept confidential . A single observer evaluated individual EPs , RNs , and NPs in one- , two- , or three-hour blocks , recording compliance with CDC h and washing recommendations . After two weeks , brightly colored signs with CDC recommendations for h and washing were posted at all sinks and a copy of a related publication on h and washing by medical personnel was distributed to all staff . H and washing behaviors were again observed . RESULTS A total of 252 situations requiring h and washing were observed , 132 pre-intervention and 120 post-intervention . Total h and washing , h and washing by each staff design ation , and h and washing in each CDC recommendation category -- except h and washing between contacts with different patients --all showed tendencies toward improvement , though none was significant ( p > 0.05 ) . Both the NPs and RNs demonstrated significantly higher adherence to recommended h and washing between patients after the intervention than did the EPs ( 85 % vs 71 % vs 31 % , p < 0.01 and p < 0.05 , respectively ) . CONCLUSION Despite a trend in improvement of compliance with CDC recommendations , h and washing among ED personnel remained unacceptably low BACKGROUND Improving h and hygiene compliance is still a major challenge for most hospitals . Innovative approaches are needed . OBJECTIVE We tested whether an innovative , theory based , team and leaders-directed strategy would be more effective in increasing h and hygiene compliance rates in nurses than a literature based state-of-the-art strategy . DESIGN AND SETTING A cluster r and omised controlled trial called HELPING H AND S was conducted in 67 nursing wards of three hospitals in the Netherl and s. PARTICIPANTS All affiliated nurses of the nursing wards . Wards were r and omly assigned to either the team and leaders-directed strategy ( 30 wards ) or the state-of-the-art strategy ( 37 wards ) . METHODS The control arm received a state-of-the-art strategy including education , reminders , feedback and targeting adequate products and facilities . The experimental group received all elements of the state-of-the-art strategy supplemented with interventions based on social influence and leadership , comprising specific team and leaders-directed activities . Strategies were delivered during a period of six months . We monitored nurses ' HH compliance during routine patient care before and directly after strategy delivery , as well as six months later . Secondary outcomes were compliance with each type of h and hygiene opportunity , the presence of jewellery and whether the nurses wore long-sleeved clothes . The effects were evaluated on an intention-to-treat basis by comparing the post- strategy h and hygiene compliance rates with the baseline rates . Multilevel analysis was applied to compensate for the clustered nature of the data using mixed linear modelling techniques . RESULTS During the study , we observed 10,785 opportunities for appropriate h and hygiene in 2733 nurses . The compliance in the state-of-the-art group increased from 23 % to 42 % in the short term and to 46 % in the long run . The h and hygiene compliance in the team and leaders-directed group improved from 20 % to 53 % in the short term and remained 53 % in the long run . The difference between both strategies showed an Odds Ratio of 1.64 ( 95 % CI 1.33 - 2.02 ) in favour of the team and leaders-directed strategy . CONCLUSIONS Our results support the added value of social influence and enhanced leadership in h and hygiene improvement strategies . The methodology of the latter also seems promising for improving team performance with other patient safety issues . TRIAL REGISTRATION Clinical Trials.gov [ NCT00548015 ] Background The emergency department ( ED ) represents an environment with a high density of invasive , and thus , infection-prone procedures . The two primary goals of this study were ( 1 ) to define the number of h and -rubs needed for an individual patient care at the ED and ( 2 ) to optimize h and hygiene ( HH ) compliance without increasing workload . Methods Prospect i ve tri-phase ( 6-week observation phases interrupted by two 6-week interventions ) before after study to determine opportunities for and compliance with HH ( WHO definition ) . St and ard operating procedures ( SOPs ) were optimized for invasive procedures during two predefined intervention periods ( phases I and II ) to improve workflow practice s and thus compliance with HH . Results 378 patient cases were evaluated with 5674 opportunities for h and rubs ( HR ) and 1664 HR performed . Compliance significantly increased from 21 % ( 545/2603 ) to 29 % ( 467/1607 ) , and finally 45 % ( 652/1464 ; all p<0.001 ) in phases 1 , 2 , and 3 , respectively . The number of HR needed for one patient care significantly decreased from 22 to 13 for the non-surgical and from 13 to 7 for the surgical patients ( both p<0.001 ) due to improved workflow practice s after implementing SOPs . In parallel , the number of HR performed increased from 3 to 5 for non-surgical ( p<0.001 ) and from 2 to 3 for surgical patients ( p=0.317 ) . Avoidable opportunities as well as glove usage instead of HR significantly decreased by 70 % and 73 % , respectively . Conclusions Our study provides the first detailed data on HH in an ED setting . Importantly , HH compliance improved significantly without increasing workload OBJECTIVE To quantify the Hawthorne effect of h and hygiene performance among healthcare workers using direct observation . DESIGN Prospect i ve observational study . SETTING Intensive care unit , university hospital . METHODS Direct observation of h and hygiene compliance over 48 audits of 2 hours each . Simultaneously , h and hygiene events ( HHEs ) were recorded using electronic alcohol-based h and rub dispensers . Directly observed and electronically recorded HHEs during the 2 hours of direct observation were compared using Spearman correlations and Bl and -Altman plots . To quantify the Hawthorne effect , we compared the number of electronically recorded HHEs during the direct observation periods with the re-scaled electronically recorded HHEs in the 6 remaining hours of the 8-hour working shift . RESULTS A total of 3,978 opportunities for h and hygiene were observed during the 96 hours of direct observation . H and hygiene compliance was 51 % ( 95 % CI , 49%-53 % ) . There was a strong positive correlation between directly observed compliance and electronically recorded HHEs ( ρ=0.68 [ 95 % CI , 0.49 - 0.81 ] , P<.0001 ) . In the 384 hours under surveillance , 4,180 HHEs were recorded by the electronic dispensers . Of those , 2,029 HHEs were recorded during the 96 hours in which direct observation was also performed , and 2,151 HHEs were performed in the remaining 288 hours of the same working shift that were not under direct observation . Healthcare workers performed 8 HHEs per hour when not under observation compared with 21 HHEs per hour during observation . CONCLUSIONS Directly and electronically observed HHEs were in agreement . We observed a marked influence of the Hawthorne effect on h and hygiene performance BACKGROUND H and hygiene prevents cross infection in hospitals , but compliance with recommended instructions is commonly poor . We attempted to promote h and hygiene by implementing a hospital-wide programme , with special emphasis on bedside , alcohol-based h and disinfection . We measured nosocomial infections in parallel . METHODS We monitored the overall compliance with h and hygiene during routine patient care in a teaching hospital in Geneva , Switzerl and , before and during implementation of a h and -hygiene campaign . Seven hospital-wide observational surveys were done twice yearly from December , 1994 , to December , 1997 . Secondary outcome measures were nosocomial infection rates , attack rates of methicillin-resistant Staphylococcus aureus ( MRSA ) , and consumption of h and rub disinfectant . FINDINGS We observed more than 20,000 opportunities for h and hygiene . Compliance improved progressively from 48 % in 1994 , to 66 % in 1997 ( p<0.001 ) . Although recourse to h and washing with soap and water remained stable , frequency of h and disinfection substantially increased during the study period ( p<0.001 ) . This result was unchanged after adjustment for known risk factors of poor adherence . H and hygiene improved significantly among nurses and nursing assistants , but remained poor among doctors . During the same period , overall nosocomial infection decreased ( prevalence of 16.9 % in 1994 to 9.9 % in 1998 ; p=0.04 ) , MRSA transmission rates decreased ( 2.16 to 0.93 episodes per 10,000 patient-days ; p<0.001 ) , and the consumption of alcohol-based h and rub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 ( p<0.001 ) . INTERPRETATION The campaign produced a sustained improvement in compliance with h and hygiene , coinciding with a reduction of nosocomial infections and MRSA transmission . The promotion of bedside , antiseptic h and rubs largely contributed to the increase in compliance OBJECTIVE To evaluate the effects of a h and hygiene program on compliance with h and hygiene and the rate of nosocomial infections in a neonatal intensive care unit ( NICU ) . DESIGN Open trial . SETTING A level-III NICU in a teaching hospital . PARTICIPANTS Nurses , physicians , and other healthcare workers in the NICU . INTERVENTIONS A multimodal campaign for h and hygiene promotion was conducted beginning in September 1998 . This program consisted of formal lectures , written instructions and posted reminders regarding h and hygiene and proper h and washing techniques , covert observation , financial incentives , and regular group feedback on compliance . Surveillance of h and washing compliance and nosocomial infections before and during the program was analyzed . RESULTS Overall compliance with h and hygiene improved from 43 % at baseline to 80 % during the promotion program . The rate of nosocomial infections decreased from 15.13 to 10.69 per 1,000 patient-days ( P = .003 ) with improved h and washing compliance . In particular , respiratory tract infections decreased from 3.35 to 1.06 per 1,000 patient-days during the h and washing campaign ( P = .002 ) . Furthermore , the correlation between nosocomial infection of the respiratory tract and h and washing compliance also reached statistical significance ( r = -0.385 ; P = .014 ) . CONCLUSIONS Improved compliance with h and washing was associated with a significant decrease in overall rates of nosocomial infection and respiratory infections in particular . Washing h and s is a simple , economical , and effective method for preventing nosocomial infections in the NICU Nosocomial infections are serious complications among preterm infants admitted to neonatal intensive care units ( NICU ) . H and hygiene is one of the most effective measures to prevent these infections . This study , performed in a tertiary level NICU , highlights the importance of a multimodal intervention program for adherence to h and hygiene . The compliance with h and hygiene among health care workers of the NICU increased significantly from 23 % in the baseline assessment to 50 % in the second assessment and the incidence of sepsis decreased from 13.4 % to 11.3 % after implementation of an intervention program BACKGROUND Although h and hygiene is the most important measure in the prevention of nosocomial infection , adherence to recommendations among health care workers ( HCW ) is low . Evaluation of compliance with h and hygiene was carried out in a Spanish teaching hospital . METHODS In 2005 , adherence to h and hygiene was evaluated hospital wide through direct observation , collecting data on h and hygiene carried out whenever indicated ( opportunity for h and hygiene ) . Compliance was defined as h and washing/disinfection in an opportunity for h and hygiene according to hospital protocol s. The results were analyzed using mixed effects models , with the HCW observed as the r and om effect . RESULTS A total of 1254 opportunities for h and hygiene were observed in 247 HCWs . Mean compliance was 20 % . Although few differences were observed among types of HCW , compliance varied according to hospital area ( 69 % in the intensive care unit [ ICU ] ) and timing with respect to patient contact ( compliance after contact was twice that before contact ) . Multivariate analyses revealed a protective odds ratio ( OR ) for nonadherence in ICUs ( OR , 0.04 ; 95 % confidence interval ( 95 % CI ) : 0.01 - 0.10 ) and after patient contact ( OR , 0.25 ; 95 % CI : 0.17 - 0.38 ) . CONCLUSION Low adherence observed suggests that new interventions should focus in modification of HCWs ' habits and attitudes , working at several levels : individual and institutional There are few data measuring rates of contact by healthcare workers ( HCWs ) with intensive care unit ( ICU ) patients ( direct contacts ) and their immediate environment ( indirect contacts ) , or estimates of the time needed for 100 % h and hygiene compliance . We measured this using a prospect i ve trained observer study in a 12-bedded UK adult general ICU admitting > 600 mixed medical/surgical patients annually . HCWs were observed in ICU bed spaces for 1-h periods by a single research er using a pre-determined plan , such that all 12 beds were observed for similar times and throughout the day . Mean daily rates of direct and indirect contact between HCWs and ICU patients were calculated . Observed post-contact h and hygiene compliance was also measured . Numbers of contacts/day that were or were not followed by h and hygiene , and estimates of the time needed daily for 100 % compliance were calculated . On average , each patient was contacted directly 159 [ 95 % confidence intervals ( CI ) 144 - 178 ] times and contacted indirectly 191 ( 95 % CI 174 - 210 ) times/day . Observed post-contact h and hygiene rates were 43 % for direct contacts and 12 % for indirect contacts . Staff contacting more than one patient during routine care , who carry the highest risk of transmitting infection between patients , made , on average , 22 direct and 107 indirect contacts without adequate h and hygiene/patient/day . One hundred percent h and hygiene compliance by all healthcare workers would require about 230 min/patient/day ( 100 min for direct and 130 min for indirect contacts ) BACKGROUND H and hygiene ( HH ) is critical to infection control , but compliance is low . Alcohol-based antiseptics may improve HH . HH practice s in Russia are not well described , and facilities are often inadequate . SETTING Four 6-bed units in a neonatal intensive care unit in St. Petersburg , Russia . METHODS Prospect i ve surveillance of HH compliance , nosocomial colonization , and antibiotic administration was performed from January until June 2000 . In February 2000 , alcohol-based h and rub was provided for routine HH use . Eight weeks later , a quality improvement intervention was implemented , consisting of review of interim data , identification of opinion leaders , posting of colonization incidence rates , and regular feedback . Means of compliance , colonization , and antibiotic use were compared for periods before and after each intervention . RESULTS A total of 1,027 events requiring HH were observed . Compliance was 44.2 % before the first intervention , 42.3 % between interventions , and 48 % after the second intervention . Use of alcohol rose from 15.2 % of HH indications to 25.2 % between interventions and 41.5 % after the second intervention . The incidence of nosocomial colonization ( per 1,000 patient-days ) with Klebsiella pneumoniae was initially 21.5 , decreased to 4.7 , and then was 3.2 in the final period . Rates of antibiotic and device use also decreased . CONCLUSIONS HH may have increased slightly , but the largest effect was a switch from soap and water to alcohol which may have been associated with decreased cross-transmission of Klebsiella , although this may have been confounded by lower device use . Alcohol-based antiseptic may be an improvement over current practice s , but further research is required This observational study measured healthcare workers ' ( HCWs ' ) , patients ' and visitors ' h and hygiene compliance over a 24h period in two hospital wards using the ' five moments of h and hygiene ' observation tool . H and hygiene is considered to be the most effective measure in reducing healthcare-associated infections but studies have reported suboptimal levels of compliance . Most studies have used r and om observational time-periods for data collection and this has been criticised . We monitored a total of 823 h and hygiene opportunities ( HCWs , N=659 ; patients and visitors , N=164 ) . Among HCWs , compliance was 47 % for doctors , 75 % for nurses , 78 % for allied health professionals , and 59 % for ancillary and other staff ( P<0.001 ) . There was no difference in compliance between patients and visitors ( 56 % vs 57 % , P=0.87 ) . H and hygiene compliance varied depending on which of the five moments of hygiene HCWs had undertaken ( P<0.001 ) , with compliance before an aseptic task being 100 % ( 3/3 ) ; after body fluid exposure 93 % ( 86/93 ) ; after patient contact 80 % ( 114/142 ) ; before patient contact 68 % ( 196/290 ) ; and after contact with surroundings 50 % ( 65/129 ) . Lower levels of compliance were found for HCWs working during the early shift ( P<0.001 ) . For patients and visitors there was no evidence of an association between moments of hygiene and compliance . Levels of compliance were higher compared with previous reported estimates . Medical staff had the lowest level of compliance and this continues to be a concern which warrants specific future interventions OBJECTIVES Adherence to h and hygiene among healthcare workers ( HCWs ) is widely believed to be a key factor in reducing the spread of healthcare-associated infection . The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to h and hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus ( MRSA ) colonization . DESIGN Cluster-r and omized controlled trial . SETTING Thirty hospital units in 3 tertiary care hospitals in Hamilton , Ontario , Canada . INTERVENTION After a 3-month baseline period of data collection , 15 units were r and omly assigned to the intervention arm ( with performance feedback , small-group teaching seminars , and posters ) and 15 units to usual practice . H and hygiene was observed during r and omly selected 15-minute periods on each unit , and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008 . RESULTS We found that 3,812 ( 48.2 % ) of 7,901 opportunities for h and hygiene in the intervention group result ed in adherence , compared with 3,205 ( 42.6 % ) of 7,526 opportunities in the control group ( P < .001 ; independent t test ) . There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group . CONCLUSION Among HCWs in Ontario tertiary care hospitals , the rate of adherence to h and hygiene had a statistically significant increase of 6 % with a multifaceted intervention , but the incidence of MRSA colonization was not reduced H and hygiene is considered to be the single most effective measure to prevent healthcare-associated infection . Although there have been several reports on h and hygiene compliance , data on patients with multidrug-resistant ( MDR ) organisms in special isolation conditions are lacking . Therefore , we conducted a prospect i ve observational study of indications for , and compliance with , h and hygiene in patients colonised or infected with meticillin-resistant Staphylococcus aureus ( MRSA ) or extended-spectrum β-lactamase (ESBL)-producing enterobacteria in surgical intensive and intermediate care units . H and disinfectant used during care of patients with MRSA was measured . Observed daily h and hygiene indications were higher in MRSA isolation conditions than in ESBL isolation conditions . Observed compliance rates were 47 % and 43 % for the MRSA group and 54 % and 51 % for the ESBL group in the surgical intensive care unit and the intermediate care unit , respectively . Compliance rates before patient contact or aseptic tasks were significantly lower ( 17 - 47 % ) than after contact with patient , body fluid or patient 's surroundings ( 31 - 78 % ) . Glove usage instead of disinfection was employed in up to 100 % before patient contact . However , compliance rates calculated from disinfectant usage were two-fold lower ( intensive care : 24 % vs 47 % ; intermediate care : 21 % vs 43 % ) . This study is the first to provide data on h and hygiene in patients with MDR bacteria and includes a comparison of observed and calculated compliance . Compliance is low in patients under special isolation conditions , even for the indications of greatest impact in preventing healthcare-associated infections . These data may help to focus measures to reduce transmission of MDR bacteria and improve patient safety A one-year prospect i ve study of 454 patients in a pediatric intensive care unit was performed to determine whether the rate of breaks in h and washing technique was different between medical professionals and to determine whether these rates were altered by the use of the overgown . A h and washing break in technique was defined as not washing your h and s after direct contact with either patients or support equipment before contact with another patient or departure from the unit . Ninety-four two-hour sessions were monitored by a research nurse during four cross-over periods of gown and no-gown use . Physicians did not wash their h and s in 834 ( 79 % ) of 1056 contacts , nurses in 1073 ( 63 % ) of 1714 cases , occupational therapists in 21 ( 62 % ) of 34 cases , respiratory therapists in 269 ( 78 % ) of 346 cases , and radiology technicians in 59 ( 78 % ) of 76 cases . Nurses used significantly better technique when compared with physicians , respiratory therapists , and radiology technicians . Gown usage overall did not affect these breaks in h and washing technique rates . Physicians did not wash their h and s 75 % of the time when gowns were not used and 82 % of the time when gowns were used . H and washing rates were unaffected by gown use in all other professionals . H and washing remains an important but neglected method of interrupting the transmission of hospital pathogens Improvement in h and hygiene ( HH ) compliance has been associated with a decrease in the incidence of hospital-acquired infection ( HAI ) and hospital-acquired methicillin-resistant Staphylococcus aureus ( HA-MRSA ) infection/colonization . We aim ed to evaluate the impact of a multimodal intervention in medical wards on HH compliance , alcohol-based h and rub ( AHR ) consumption and incidence of HAI and HA-MRSA . A before-after intervention study and an assessment 1 year later were conducted in three internal medicine wards . HH compliance during routine patient care was monitored using the WHO HH observation method . AHR consumption was registered . HAI incidence was actively sought during the PRE and POST periods . HAI risk factors were prospect ively recorded and incidence density was calculated . A total of 825 patients were prospect ively followed in the PRE period and 868 patients in the POST period . We observed 1531 opportunities for HH in PRE and POST periods and 450 1 year later . HH compliance improved from 54.3 % to 75.8 % ( p 0.005 ) and remained 75.8 % at follow-up . AHR consumption increased from 10.5 to 27.2 L/1000 hospital-days and 31.5 L/1000 hospital-days at follow-up . Incidence density of HAI was 6.93 and 6.96/1000 hospital-days in the PRE and POST intervention periods , respectively . HA-MRSA incidence density was 0.92 in the PRE period vs. 0.25/1000 hospital-days in the POST period ( p 0.2 ) and 0.15/1000 hospital-days ( p 0.1 ) 1 year later . A sustained increase in AHR consumption was followed by an improvement in HH compliance after a multimodal campaign . A trend for lower incidence density of new hospital-acquired MRSA was detected in the POST intervention and follow-up periods CONTEXT Under routine hospital conditions h and washing compliance of health care workers including nurses , physicians , and others ( eg , physical therapists and radiologic technicians ) is unacceptably low . OBJECTIVES To investigate the efficacy of an education/ feedback intervention and patient awareness program ( cognitive approach ) on h and washing compliance of health care workers ; and to compare the acceptance of a new and increasingly accessible alcohol-based waterless h and disinfectant ( technical approach ) with the st and ard sink/soap combination . DESIGN A 6-month , prospect i ve , observational study . SETTING One medical intensive care unit ( ICU ) , 1 cardiac surgery ICU , and 1 general medical ward located in a 728-bed , tertiary care , teaching facility . PARTICIPANTS Medical caregivers in each of the above setting s. INTERVENTIONS Implementation of an education/ feedback intervention program ( 6 in-service sessions per each ICU ) and patient awareness program , followed by a new , increasingly accessible , alcohol-based , waterless h and antiseptic agent , initially available at a ratio of 1 dispenser for every 4 patients and subsequently 1 for each patient . MAIN OUTCOME MEASURE Direct observation of h and -washing for 1575 potential opportunities monitored over 120 hours r and omized for both time of day and bed locations . RESULTS Baseline h and washing compliance before and after defined events was 9 % and 22 % for health care workers in the medical ICU and 3 % and 13 % for health care workers in the cardiac surgery ICU , respectively . After the education/feedback intervention program , h and washing compliance changed little ( medical ICU , 14 % [ before ] and 25 % [ after ] ; cardiac surgery ICU , 6 % [ before ] and 13 % [ after ] ) . Observations after introduction of the new , increasingly accessible , alcohol-based , waterless h and antiseptic revealed significantly higher h and washing rates ( P<.05 ) , and h and washing compliance improved as accessibility was enhanced-before 19 % and after 41 % with 1 dispenser per 4 beds ; and before 23 % and after 48 % with 1 dispenser for each bed . CONCLUSIONS Education/feedback intervention and patient awareness programs failed to improve h and washing compliance . However , introduction of easily accessible dispensers with an alcohol-based waterless h and washing antiseptic led to significantly higher h and washing rates among health care workers BACKGROUND H and hygiene is considered to be the single most effective tool to prevent health care-associated infections . Daily h and hygiene opportunities and compliance for pediatric/neonatal intensive care units ( ICU ) are currently unknown . METHODS This was a prospect i ve observational study in pediatric and neonatal ICU patients with analyses of h and hygiene behavior in relation to profession , indication , and shift and correlation with disinfectant usage . RESULTS H and hygiene opportunities were significantly higher for pediatric ( 321/24 hours ) than neonatal ( 194/24 hours ; P = .024 ) patients . Observed compliance rates were 53 % ( pediatric ) and 61 % ( neonatal ) and found to be significantly higher in nurses ( 57 % ; 66 % ) than in physicians ( 29 % , 52 % , respectively ; P < .001 ; P = .017 , respectively ) . For neonates , compliance rates were significantly higher before patient contact and aseptic tasks ( 78 % ) than after patient , patient body fluid , or patients ' surrounding contact ( 57 % ; P < .001 ) . Calculating disinfectant usage revealed a 3-fold lower compliance rate of 17 % . CONCLUSION This study provides the first data on opportunities for and compliance with h and hygiene in pediatric/neonatal patients encompassing the whole day and night activities and including a comparison of observed and calculated compliance rates . Observation revealed high compliance especially in nurses and in situations of greatest impact . The data provide a detailed characterization of h and hygiene performance in the neonatal/pediatric ICU setting PURPOSE Healthcare-associated infections ( HCAIs ) impact 10 % of hospitalized patients . Some of these infections result from bacterial cross contamination and poor compliance with guidelines ( Pittet D : Compliance with h and disinfection and its impact on hospital-acquired infections . J HospInfect 48 Suppl A : S40-S46 , 2001 ) ; ( Watanakunakorn C , Wang C , Hazy J : An observational study of h and washing and infection control practice s by healthcare workers . Infect Control Hosp Epidemiol 19:858 - 860 , 1998 ) . Contamination of provider h and s may be a modifiable risk factor . We instituted a novel multimodal system design ed to improve h and hygiene by ICU providers . MATERIAL S AND METHODS A before and after study design was used to evaluate the impact on the incidence of CRBSI and VAP of a multi-modal program incorporating education , performance feedback , and a body worn h and hygiene device . Compliance was communicated quarterly . Primary outcomes were CRBSIs and VAPs per 1,000 line days or per 1,000 ventilator days and compliance rates . Secondary outcomes were hospital length of stay and mortality . RESULTS A total of 1 , 262 and 1,331 patients were evaluated during consecutive 12 month periods . VAP per 1000 vent days were significantly reduced after introduction of the program [ 3.7 vs. 6.9 ] P < .01 . The reduction in CRBSI per 1000 line days was not significant [ 1.5 vs. 2.6 ] , P = .09 . Observed h and hygiene increased during the study period . There was no significant difference in mortality . CONCLUSIONS A novel multi-modal h and hygiene system result ed in a reduction in VAP . Provider h and contamination during patient care in the ICU is a modifiable risk factor for reducing ventilator associated pneumonias Various electronic tools have been developed to monitor h and hygiene compliance ( HHC ) . A prospect i ve , investigator-blinded , pilot study was conducted to evaluate the feasibility and effectiveness of an electronic h and hygiene feedback device to improve rates of h and hygiene . The first month of participation provided baseline rates of HHC ( 37 % ) . During months 2 - 5 , mean HHC rates were 43 % , 44 % , 45 % , and 49 % respectively ( P < 0.001 ) . Implementing this electronic device was feasible and showed a modest improvement in rates of HHC . Subsequent studies are warranted to vali date the impact of such electronic devices on a larger scale |
497 | 30,499,231 | Nonetheless , probiotics seem to potentially produce a significant therapeutic effect for subjects with pre-existing depressive symptoms . | Depression is one of the most prevalent mental illnesses and is often associated with various other medical disorders .
Since the 1980s , the primary pharmacological treatment has been antidepressants , but due to the recent discovery of the association between the gut microbiome and mental health , probiotics have been proposed as an adjunctive or alternate treatment .
In this narrative review , we aim to provide a holistic perspective by synthesizing and evaluating existing evidence , discussing key biological mechanisms , exploring the history of probiotic use , and appreciating the influence of modern diet on mental health . | Stress plays an important role in the development of symptoms contributing to disease . Stress induces various disorders with gastrointestinal , physical , and psychological symptoms . Probiotics can help regulate or modulate gastrointestinal functions . The aim of the present study was to investigate the effects of a probiotic preparation ( Probio-Stick ) on stress-induced symptoms in volunteers . A double-blind , placebo-controlled , r and omized study was conducted on volunteers with symptoms of stress . Subjects received a probiotic ( Probio-Stick ; Lallem and SAS , Saint-Simon , France ) containing Lactobacillus acidophilus Rosell-52 and Bifidobacterium longum Rosell-175 ( 3 x 10(9 ) colony-forming units per sachet stick ) or a sensorially identical placebo without probiotics during a 3-week period . The consumption of probiotics significantly reduced 2 stress-induced gastrointestinal symptoms ( abdominal pain and nausea/vomiting ) for intention-to-treat or per- protocol population s. In contrast , the probiotics did not significantly modify the other physical and psychological symptoms and sleep problems induced by stressful life events for intention-to-treat or per- protocol population s. The results indicate that Probio-Stick can provide a beneficial effect on the gastrointestinal symptoms experienced by individuals affected by chronic stress Objective : The impact on mood and memory of consuming a probiotic containing milk drink , or a placebo , was examined as , previously , a poor mood has been found to correlate with the frequency of constipation . Design : A double-blind placebo-controlled trial with r and om allocation of subjects . Setting : Subjects went about their normal life in the community apart from three visits to the laboratory . Subjects : One hundred and thirty-two healthy members of general population , mean age 61.8 years , volunteered in response to local media coverage . One hundred and twenty-four finished the trial . Intervention : For a 3-week period , either a probiotic containing milk drink , or a placebo , were consumed daily . Mood and cognition were measured at baseline , and after 10 and 20 days of consumption . Results : At baseline those who reported themselves to be less frequently constipated were more clearheaded , confident and elated . Although the taking of the probiotic did not generally change the mood , this appeared to be a reflection of the generally good mood in this sample . When those in the bottom third of the depressed/elated dimension at baseline were considered , they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic . The intervention did not , however , influence the reported frequency of defaecation , probably a reflection of the initially low incidence of constipation . An unexpected and possibly chance finding was that the consumption of probiotics result ed in a slightly-poorer performance on two measures of memory . Conclusions : The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor . This improvement in mood was not , however , associated with an increased frequency of defaecation . Sponsorship : Funded by Yakult , Japan Oral intake of Lactobacillus pentosus strain b240 ( b240 ) has been shown to enhance the secretion of salivary secretory IgA in elderly adults . However , its clinical benefits remain to be determined . We tested the hypothesis that b240 exerts a protective effect against the common cold in elderly adults . The design of the present study was a r and omised , double-blind , placebo-controlled trial ( RCT ) with parallel three-group comparison . For this purpose , 300 eligible elderly adults were r and omly allocated to one of three groups , namely a placebo , low-dose or high-dose b240 group . Participants in the low-dose and high-dose b240 groups were given tablets containing 2 × 10(9 ) or 2 × 10(10 ) cells , respectively , of heat-killed b240 , while those in the placebo group were given tablets without b240 . Each group consumed their respective tablets once daily for 20 weeks . The common cold was assessed on the basis of a diary . Change in quality of life was evaluated using the SF-36 . Of the total participants , 280 completed the 20-week RCT . The accumulated incidence rate of the common cold was 47·3 , 34·8 and 29·0 % for the placebo , low-dose b240 and high-dose b240 groups , respectively ( P for trend = 0·012 ) . Lower incidence rates were consistently observed throughout the experimental period in the b240 groups ( log-rank test , P= 0·034 ) . General health perception , as determined by the SF-36 ® , dose-dependently increased in the b240 groups ( P < 0·025 ) . In conclusion , oral intake of b240 significantly reduced the incidence rate of the common cold in elderly adults , indicating that b240 might be useful in improving resistance against infection through mucosal immunity BACKGROUND : Probiotic bacteria exhibit a variety of properties , including immunomodulatory activity , which are unique to a particular strain . Thus , not all species will necessarily have the same therapeutic potential in a particular condition . We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome ( IBS ) . OBJECTIVES : This study was design ed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale , multicenter , clinical trial of women with IBS . A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation . METHODS : After a 2-wk baseline , 362 primary care IBS patients , with any bowel habit subtype , were r and omized to either placebo or freeze-dried , encapsulated B. infantis at a dose of 1 × 106 , 1 × 108 , or 1 × 1010 , cfu/mL for 4 wk . IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort . A composite symptom score , the subject 's global assessment of IBS symptom relief , and measures of quality of life ( using the IBS-QOL instrument ) were also recorded . RESULTS : B. infantis 35624 at a dose of 1 × 108 cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating , bowel dysfunction , incomplete evacuation , straining , and the passage of gas at the end of the 4-wk study . The improvement in global symptom assessment exceeded placebo by more than 20 % ( p < 0.02 ) . Two other doses of probiotic ( 1 × 106 and 1 × 1010 ) were not significantly different from placebo ; of these , the 1 × 1010 dose was associated with significant formulation problems . No significant adverse events were recorded . CONCLUSIONS : B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS . At a dosage level of 1 × 108 cfu , it can be delivered by a capsule making it stable , convenient to administer , and amenable to widespread use . The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice BACKGROUND & AIMS Probiotics can reduce symptoms of irritable bowel syndrome ( IBS ) , but little is known about their effects on psychiatric comorbidities . We performed a prospect i ve study to evaluate the effects of Bifidobacterium longum NCC3001 ( BL ) on anxiety and depression in patients with IBS . METHODS We performed a r and omized , double-blind , placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern ( based on Rome III criteria ) and mild to moderate anxiety and /or depression ( based on the Hospital Anxiety and Depression scale ) at McMaster University in Canada , from March 2011 to May 2014 . At the screening visit , clinical history and symptoms were assessed and blood sample s were collected . Patients were then r and omly assigned to groups and given daily BL ( n = 22 ) or placebo ( n = 22 ) for 6 weeks . At weeks 0 , 6 , and 10 , we determined patients ' levels of anxiety and depression , IBS symptoms , quality of life , and somatization using vali date d question naires . At weeks 0 and 6 , stool , urine and blood sample s were collected , and functional magnetic resonance imaging ( fMRI ) test was performed . We assessed brain activation patterns , fecal microbiota , urine metabolome profiles , serum markers of inflammation , neurotransmitters , and neurotrophin levels . RESULTS At week 6 , 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale , vs 7 of 22 patients in the placebo group ( P = .04 ) . BL had no significant effect on anxiety or IBS symptoms . Patients in the BL group had a mean increase in quality of life score compared with the placebo group . The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas , including amygdala and fronto-limbic regions , compared with placebo . The groups had similar fecal microbiota profiles , serum markers of inflammation , and levels of neurotrophins and neurotransmitters , but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites . At week 10 , depression scores were reduced in patients given BL vs placebo . CONCLUSION In a placebo-controlled trial , we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS . These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity . Clinical Trials.gov no. NCT01276626 Objectives : This trial investigated whether probiotics improved mood , stress and anxiety in a sample selected for low mood . We also tested whether the presence or severity of irritable bowel syndrome symptoms , and levels of proinflammatory cytokines , brain-derived neurotrophic factor and other blood markers , would predict or impact treatment response . Method : Seventy-nine participants ( 10 dropouts ) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were r and omly allocated to receive either a probiotic preparation ( containing Lactobacillus helveticus and Bifidobacterium longum ) or a matched placebo , in a double-blind trial for 8 weeks . Data were analysed as intent-to-treat . Results : No significant difference was found between the probiotic and placebo groups on any psychological outcome measure ( Cohen ’s d range = 0.07–0.16 ) or any blood-based biomarker . At end-point , 9 ( 23 % ) of those in the probiotic group showed a ⩾60 % change on the Montgomery – Åsberg Depression Rating Scale ( responders ) , compared to 10 ( 26 % ) of those in the placebo group ( χ 1 2 = 0 . 107 , p = ns ) . Baseline vitamin D level was found to moderate treatment effect on several outcome measures . Dry mouth and sleep disruption were reported more frequently in the placebo group . Conclusions : This study found no evidence that the probiotic formulation is effective in treating low mood , or in moderating the levels of inflammatory and other biomarkers . The lack of observed effect on mood symptoms may be due to the severity , chronicity or treatment resistance of the sample ; recruiting an antidepressant-naive sample experiencing mild , acute symptoms of low mood , may well yield a different result . Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective . Vitamin D levels should be monitored in future studies in the area . The results of this trial are preliminary ; future studies in the area should not be discouraged BACKGROUND & AIMS Changes in gut microbiota have been reported to alter signaling mechanisms , emotional behavior , and visceral nociceptive reflexes in rodents . However , alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans . We investigated whether consumption of a fermented milk product with probiotic ( FMPP ) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks . METHODS Healthy women with no gastrointestinal or psychiatric symptoms were r and omly assigned to groups given FMPP ( n = 12 ) , a nonfermented milk product ( n = 11 , controls ) , or no intervention ( n = 13 ) twice daily for 4 weeks . The FMPP contained Bifidobacterium animalis subsp Lactis , Streptococcus thermophiles , Lactobacillus bulgaricus , and Lactococcus lactis subsp Lactis . Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity . Multivariate and region of interest analyses were performed . RESULTS FMPP intake was associated with reduced task-related response of a distributed functional network ( 49 % cross-block covariance ; P = .004 ) containing affective , viscerosensory , and somatosensory cortices . Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity , which could explain the observed differences in activity during the task . CONCLUSIONS Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation In a previous clinical study , a probiotic formulation ( PF ) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) decreased stress-induced gastrointestinal discomfort . Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress . The aim of the present study was to investigate the anxiolytic-like activity of PF in rats , and its possible effects on anxiety , depression , stress and coping strategies in healthy human volunteers . In the pre clinical study , rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test , a screening model for anti-anxiety agents . In the clinical trial , volunteers participated in a double-blind , placebo-controlled , r and omised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist ( HSCL-90 ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Perceived Stress Scale , the Coping Checklist ( CCL ) and 24 h urinary free cortisol ( UFC ) . Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats ( P < 0·05 ) and alleviated psychological distress in volunteers , as measured particularly by the HSCL-90 scale ( global severity index , P < 0·05 ; somatisation , P < 0·05 ; depression , P < 0·05 ; and anger-hostility , P < 0·05 ) , the HADS ( HADS global score , P < 0·05 ; and HADS-anxiety , P < 0·06 ) , and by the CCL ( problem solving , P < 0·05 ) and the UFC level ( P < 0·05 ) . L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers OBJECTIVES Rheumatoid arthritis ( RA ) is an inflammatory autoimmune disease in which the gut microbiota is altered . Probiotics are microorganisms that can normalize gut microbiota ; thus , they may help to alleviate RA symptoms . The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA . METHODS Forty-six patients with RA were assigned into two groups in this r and omized , double-blind , placebo-controlled clinical trial . The patients in the probiotic group received a daily capsule that contained a minimum of 10(8 ) colony-forming units of Lactobacillus casei 01 for 8 wk . The placebo group took capsules filled with maltodextrin for the same time period . Question naires , anthropometric measurements , and fasting blood sample s were collected , and the participants were assessed by a rheumatologist at baseline and at the end of the trial . RESULTS Disease activity score was significantly decreased by the intervention , and there was a significant difference between the two groups at the end of the study ( P < 0.01 ) . Three of the assessed serum proinflammatory cytokines ( tumor necrosis factor-α , interleukin-6 , and interleukin-12 ) significantly decreased in the probiotic group ( P < 0.05 ) ; however , serum levels of interleukin-1 β were not significantly affected by the probiotic ( P = 0.22 ) . The serum level of regulatory cytokine ( interleukin-10 ) was increased by the supplementation ( P < 0.05 ) . The proportion of interleukin-10 to interleukin-12 was significantly increased in the probiotic group as well . CONCLUSIONS L. casei 01 supplementation improved the disease activity and inflammatory status of patients with RA . Further studies are warranted to confirm these results , and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population Acute psychological stress is positively associated with a cold/flu . The present r and omised , double-blind , placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students ( n 581 ) who received Lactobacillus helveticus R0052 , Bifidobacterium longum ssp . infantis R0033 , Bifidobacterium bifidum R0071 or placebo . On each day , participants recorded the intensity ( scale : 0 = not experiencing to 3 = very intense ) for nine cold/flu symptoms , and a sum of symptom intensity > 6 was design ated as a day of cold/flu . B. bifidum result ed in a greater proportion of healthy days than placebo ( P≤ 0·05 ) . The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo ( P < 0·05 ) . There were no effects of B. infantis or L. helveticus compared with placebo on either outcome . A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes . The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep . Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress Chronic fatigue syndrome ( CFS ) is complex illness of unknown etiology . Among the broad range of symptoms , many patients report disturbances in the emotional realm , the most frequent of which is anxiety . Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora . Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans . In this pilot study , 39 CFS patients were r and omized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota ( LcS ) or a placebo daily for two months . Patients provided stool sample s and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention . We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS , and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls ( p = 0.01 ) . These results lend further support to the presence of a gut-brain interface , one that may be mediated by microbes that reside or pass through the intestinal tract In a recent clinical study , we demonstrated in the general population that Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) taken in combination for 30 days decreased the global scores of hospital anxiety and depression scale ( HADs ) , and the global severity index of the Hopkins symptoms checklist ( HSCL-90 ) , due to the decrease of the sub-scores of somatization , depression and anger-hostility spheres . Therefore , oral intake of PF showed beneficial effects on anxiety and depression related behaviors in human volunteers . From there , it is interesting to focus on the role of this probiotic formulation in the subjects with the lowest urinary free cortisol levels at baseline . This addendum presents a secondary analyse of the effects of PF in a sub- population of 25 subjects with urinary free cortisol ( UFC ) levels less than 50 ng/ml at baseline , on psychological distress based on the percentage of change of the perceived stress scale ( PSs ) , the HADs and the HSCL-90 scores between baseline and follow-up . The data show that PF improves the same scores as in the general population ( the HADs global score , the global severity index of the HSCL-90 and three of its sub-scores , i.e. somatization , depression and anger-hostility ) , as well as the PSs score and three other sub-scores of the HSCL-90 , i.e. " obsessive compulsive " , " anxiety " , and " paranoid-ideation " . Moreover , in the HSCL-90 , the score of the Factor 1 , related to anxiety and depression , is significantly improved over time in PF-treated subjects compared with controls . Additional pre clinical data showed that PF formulation does not induce side effects such as addiction or learning and memory impairments , and therefore displays a good safety profile . Complementary hypothetical mechanisms of action are proposed to explain the functioning of the brain-gut axis , particularly the relationship between probiotics and stress-related psychopathologies , such as anxiety and depression Background Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults . Thus , therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality . Objective The aim of this double-blinded , r and omized , placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults . Methods The study enrolled general older adults ( > 65 years ) . After eligibility screening qualified subjects ( n = 290 ) participated in a 2-arm study design , with each arm consisting of 12 weeks of intervention of either active or placebo product . Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing , anxiety and stress . Follow up was performed at 8 and 12 weeks . Results No persistent significant effects were observed on the primary or secondary outcome parameters of the study . A modest effect was observed in the probiotic arm , were levels of stress decreased at week 8 and 12 . Similarly , we found that subjects suffering from indigestion and abdominal pain , respectively , showed a significant decrease of anxiety at week 8 after probiotic treatment , but not at week 12 . Conclusion The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri . Neither was any significant improvement in wellbeing , stress or anxiety observed . Even though the RCT had a negative outcome , the study highlights issues important to take into consideration when design ing trials among older adults . Trial registration Clinical trials.gov/NCT01837940 BACKGROUND Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression . OBJECTIVE Heightened cognitive reactivity to normal , transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions . The present study aim ed to test if a multispecies probiotic containing Bifidobacterium bifidum W23 , Bifidobacterium lactis W52 , Lactobacillus acidophilus W37 , Lactobacillus brevis W63 , Lactobacillus casei W56 , Lactobacillus salivarius W24 , and Lactococcus lactis ( W19 and W58 ) may reduce cognitive reactivity in non-depressed individuals . DESIGN In a triple-blind , placebo-controlled , r and omized , pre- and post-intervention assessment design , 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics , while 20 control participants received an inert placebo for the same period . In the pre- and post-intervention assessment , cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale . RESULTS Compared to participants who received the placebo intervention , participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood , which was largely accounted for by reduced rumination and aggressive thoughts . CONCLUSION These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood . Probiotics supplementation warrants further research as a potential preventive strategy for depression This open pilot study of vagus nerve stimulation ( VNS ™ ) in 60 patients with treatment-resistant major depressive episodes ( MDEs ) aim ed to : 1 ) define the response rate ; 2 ) determine the profile of side effects ; and , most importantly ; 3 ) establish predictors of clinical outcome . Participants were out patients with nonatypical , nonpsychotic , major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE . While on stable medication regimens , the patients completed a baseline period followed by device implantation . A 2-week , single blind , recovery period ( no stimulation ) was followed by 10 weeks of VNS . Of 59 completers ( one patient improved during the recovery period ) , the response rate was 30.5 % for the primary HRSD28 measure , 34.0 % for the Montgomery-Äsberg Depression Rating Scale ( MADRAS ) , and 37.3 % for the Clinical Global Impression-Improvement Score ( CGI-I of 1 or 2 ) . The most common side effect was voice alteration or hoarseness , 55.0 % ( 33/60 ) , which was generally mild and related to output current intensity . History of treatment resistance was predictive of VNS outcome . Patients who had never received ECT ( lifetime ) were 3.9 times more likely to respond . Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE , none responded , compared to 39.1 % of the remaining 46 patients ( p = .0057 ) . Thus , VNS appears to be most effective in patients with low to moderate , but not extreme , antidepressant resistance . Evidence concerning VNS ' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression Abstract Objective : To analyse the occurrence of multiple drug use ( polypharmacy , PP ) in the population and to identify individuals particularly prone to PP . Methods : Data were derived from the Odense Pharmacoepidemiological Data base ( OPED ) and covered all subsidised prescriptions during 1994 presented by inhabitants in the county of Funen ( n= 466 567 ) . The number of individuals concurrently using two to four drugs ( minor PP ) and five or more drugs ( major PP ) was calculated on a r and om day in 1994 . Drugs were classified according to the Anatomical Therapeutical Chemical ( ATC ) classification index . The main therapeutic class ( second level of the ATC code ) was used as an indicator for the type of health problem . A stepwise backwards logistic regression was used to identify predictors of major PP . Odds ratios were calculated for different drug classes , and the age and sex of all drug users . Results : On a r and om day , 8.3 % of the population were exposed to minor PP and 1.2 % to major PP . The prevalence of PP increased with age , and from the age of 70 years , two thirds of all drug users were PP users . Drug use was 50 % more prevalent among women than men , but over the age of 70 , the sexes did not differ in the prevalence of major PP . Many different drug combinations were found , and among major PP users ( n= 5443 ) , two thirds had their own unique drug regimen , different from all other drug users . Cardiovascular drugs and analgesics were often involved in PP among the elderly , while asthma drugs , psychotropic drugs and anti-ulcer drugs were predominant among young individuals exposed to PP . The odds ratio ( OR ) for major PP was substantially increased for individuals treated for cardiovascular diseases ( OR , 4.5 ) , anaemia ( OR , 4.1 ) and respiratory diseases ( OR , 3.6 ) . Conclusions : PP is widespread in the population . Clinicians and organisers who are responsible for quality assurance programmes should intensify their surveillance of the groups most prone to PP ( the elderly and those using analgesics or drugs for cardiovascular disease , anaemia , asthma and diabetes ) Objective : The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic – pituitary – adrenal axis in petrochemical workers . Methods : The present r and omized double-blind , placebo-controlled trial was conducted on 70 petrochemical workers . Subjects were r and omly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule ( n = 25 ) or one probiotic capsule daily + 100 g/day conventional yogurt ( n = 25 ) or 100 g/day conventional yogurt + one placebo capsule ( n = 20 ) for 6 weeks . Mental health parameters including general health question naire ( GHQ ) and depression anxiety and stress scale ( DASS ) scores were measured . Fasting blood sample s were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic – pituitary – adrenal axis . Results : After 6 weeks of intervention , a significant improvement of GHQ was observed in the probiotic yogurt ( 18.0 ± 1.5 vs. 13.5 ± 1.9 , P = 0.007 ) and in the probiotic capsule group ( 16.9 ± 1.8 vs. 9.8 ± 1.9 , P = 0.001 ) , as well as a significant improvement in DASS scores in the probiotic yogurt ( 23.3 ± 3.7 vs. 13.0 ± 3.7 , P = 0.02 ) and the probiotic capsule group ( 18.9 ± 3.2 vs. 9.4 ± 4.0 , P = 0.006 ) . However , there was no significant improvement in the conventional yogurt group ( P = 0.05 for GHQ and P = 0.08 for DASS ) . Discussion : The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers Dietary probiotics supplementation exerts beneficial health effects . Since cigarette smoking reduces natural killer ( NK ) activity , we evaluated the effect of Lactobacillus casei Shirota ( LcS ) intake on NK cytotoxic activity in male smokers . The double-blind , placebo-controlled , r and omised study was conducted on seventy-two healthy Italian blue-collar male smokers r and omly divided for daily intake of LcS powder or placebo . Before and after 3 weeks of intake , peripheral blood mononuclear cells were isolated and NK activity and CD16⁺ cells ' number were assessed . Daily LcS intake for 3 weeks significantly increased NK activity ( P < 0.001 ) . The increase in NK activity was paralleled by an increase in CD16⁺ cells ( P < 0.001 ) . Before intake , NK cytotoxic activity inversely correlated with the number of cigarettes smoked ( R - 0.064 ) . LcS intake prevented the smoke-dependent expected NK activity reduction . The analysis of the distribution of changes in smoke-adjusted NK activity demonstrated that the positive variations were significantly associated with LcS intake , while the negative variations were associated with placebo intake ( median value of distributions of differences , 20.98 lytic unit (LU)/10⁷ cells for LcS v. - 4.38 LU/10⁷ cells for placebo , P = 0.039 ) . In conclusion , 3 weeks of daily LcS intake in Italian male smokers was associated with a higher increase in cytotoxic activity and CD16⁺ cells ' number in comparison to the placebo intake group AIM To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture ( LCR35 ) in patients suffering from irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria . Patients were allocated to receive either LCR35 ( n = 25 ) at a minimum daily dose of 6 × 10(8 ) colony forming units or placebo ( n = 25 ) for 4 wk . At inclusion , after treatment and 2 wk later , patients completed the IBS severity scale . Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion . Changes were compared between groups in the whole population and in IBS subtypes ( IBS with predominance of constipation , IBS with predominance of diarrhoea , mixed IBS , unsubtyped IBS ) . The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment . The gastrointestinal quality of life question naire and the hospital anxiety and depression ( HAD ) scale were also completed . RESULTS Both groups were balanced for baseline characteristics . In 85 % of patients , stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract . In the whole population , improvements in the IBS severity score did not differ significantly between treatments with a 25 % decrease after 4-wk treatment , and a 15 % decrease from baseline 2 wk later in both groups . In IBS subgroups , statistical analysis could not be performed due to small sample size , but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea : no change in the symptom severity score was seen with the placebo after 4 wk treatment , whereas a clinical ly relevant decrease occurred with LCR35 ( -37 % vs -3 % ) . Furthermore , in spite of an increase in symptom intensity , the IBS severity score was maintained below the baseline value 2 wk later with LCR35 ( -19 % from baseline ) , whilst a slight 5 % increase from baseline was observed with placebo . In the IBS subgroup with predominance of diarrhoea only , a clinical ly relevant decrease in abdominal pain severity score ( -36 % ) was observed with LCR35 , whereas no change occurred with placebo . In mixed IBS patients , the 20 % and 30 % decreases in the IBS severity score observed after treatment with LCR35 and placebo , respectively , were maintained 2 wk later in both groups . A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation ( -41 % vs -20 % ) and unsubtyped IBS patients ( -47 % vs -17 % ) , with the same value maintained 2 wk later . In both groups , no clinical ly relevant changes were observed either for the gastrointestinal quality of life index or HAD score . Thus , these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician . CONCLUSION This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea . These preliminary results need to be confirmed in larger studies Summary Background A suppressed immune response has been documented in students under examination stress . Aims The current study aim ed to evaluate the effect of milk fermented with yogurt cultures plus Lactobacillus casei DN-114001 ( Actimel ® ) on the immune system of subjects under academic examination stress . Methods University students were allocated to one of two groups , receiving during 6 weeks ( 3 weeks prior to , as well as the 3-week duration of the examination period ) either : a ) a glass of semi-skimmed milk each day ( control group , n=63 ) or b ) two 100mL portions per day of fermented milk ( treatment group , n=73 ) . Anxiety and immunological measurements were monitored at baseline ( Phase 0 ) and study end ( Phase 1 ) . Results The results were expressed as the differences between the data obtained from Phase 0 and Phase 1 . This was calculated by subtracting Phase 1 results from the Phase 0 and it is denominated “ Treatment effect ” . Mean ( ± SE ) anxiety increased significantly ( P<0.05 ) over the 6-week study in all students , from 40.74±2.50 to 61.19±2.64 ( in percentiles ) . There was no significant treatment effect since this increase was similar in the control and the treatment groups ( 21.65±5.09 vs 19.14±3.67 , respectively ) . However , there was a significant treatment effect ( P<0.05 ) on the mean change in absolute number of lymphocytes during the 6-week study , which decreased in the control group ( –0.04±0.12 cells x 103/mm3 ) and increased in the treatment group ( 0.37±0.11 cells x 103/mm3 ) . There was also a significant treatment effect ( P<0.05 ) on the change in absolute numbers of CD56 cells during the 6-week study . Mean absolute CD56 cells significantly decreased ( P<0.05 ) in the control group ( –51.97±21.33 cells/mm3),while remaining similar in the treatment group ( 17.29±17.27 cells/mm3 ) . During the study , mean serum cortisol increased 4.30±0.98 µg/dL in the control group , and 1.75±1.05 µg/dL in the treatment group and no significant differences were found between both values ( P=0.062 ) . Conclusions Milk fermented with yogurt cultures plus Lactobacillus casei DN-114001 was able to modulate the number of lymphocytes and CD56 cells in subjects under academic examination stress |
498 | 30,387,126 | AUTHORS ' CONCLUSIONS Current evidence suggests that individual caseworker-assigned discharge plans , as compared to non-caseworker-assigned plans , may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma .
There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma , and there is an absence of data for children with other chronic respiratory conditions . | BACKGROUND Chronic respiratory conditions are major causes of mortality and morbidity .
Children with chronic health conditions have increased morbidity associated with their physical , emotional , and general well-being .
Acute respiratory exacerbations ( AREs ) are common in children with chronic respiratory disease , often requiring admission to hospital .
Reducing the frequency of AREs and recurrent hospitalisations is therefore an important goal in the individual and public health management of chronic respiratory illnesses in children .
Discharge planning is used to decide what a person needs for transition from one level of care to another and is usually considered in the context of discharge from hospital to the home .
Discharge planning from hospital for ongoing management of an illness has historically been referral to a general practitioner or allied health professional or self management by the individual and their family with limited communication between the hospital and patient once discharged .
Effective discharge planning can decrease the risk of recurrent AREs requiring medical care .
An individual caseworker-assigned discharge plan may further decrease exacerbations .
OBJECTIVES To evaluate the efficacy of individual caseworker-assigned discharge plans , as compared to non-caseworker-assigned plans , in preventing hospitalisation for AREs in children with chronic lung diseases such as asthma and bronchiectasis . | Background : The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze . Methods : A prospect i ve , r and omised , partially blinded , controlled trial was design ed at two secondary care centres . Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children 's ward or attendance at an accident and emergency department or children 's ( emergency ) assessment unit ( A&E/CAU ) with a primary diagnosis of acute severe asthma or wheezing were recruited . 101 children were r and omised into the control group and received usual care and 99 were assigned to the intervention group and received : ( 1 ) a pre-school asthma booklet ; ( 2 ) a written guided self-management plan ; and ( 3 ) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s ) and child . Subjects were assessed at 3 , 6 , and 12 months . The main outcomes were GP consultation rates , hospital re-admissions , and attendances at A&E/CAU . Secondary outcomes included disability score , caregivers ' quality of life , and parental knowledge of asthma . Results : There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures . Conclusions : These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months BACKGROUND The aim of this study was to compare the effectiveness of an intensive asthma education program ( group B ) with that of a st and ard asthma education program ( group A ) . METHODS A prospect i ve r and omized single blinded study was conducted in the pediatric department of a public hospital in Hong Kong . Children aged 2 - 15 years admitted to the pediatric department with an acute attack of asthma were recruited . A st and ard asthma education program ( group A ) or an intensive asthma education program ( group B ) for children were offered . The main outcome measures include the number of visits to the emergency department and the number of hospitalization for asthma during the 3 month follow-up period . RESULTS A total of 45 children were in group A and 55 in group B. Group B had statistically significant reductions in the number of visits to the emergency department and the number of hospitalizations . Drug compliance was also significantly improved in group B. Parents ' satisfaction rate was also higher in group B. CONCLUSION The intensive asthma education program might be more cost effective than the st and ard asthma education program in the management of asthmatic children admitted to hospital in Hong Kong PURPOSE Many asthmatic patients discharged from emergency departments do not have timely follow-up visits with a primary care physician . This study was conducted to determine the effectiveness of a health professional-based intervention in improving process of care and health outcomes among asthmatic patients discharged from emergency departments . METHODS We enrolled 125 asthmatic patients , aged 5 through 50 years , from the emergency department of a community-based hospital ; 62 patients were assigned to usual care and 63 to enhanced care . Enhanced care consisted of usual care plus employment of a coordinator to make follow-up appointments with the patient 's primary care physician with at least one reminder telephone call to the patient . RESULTS At 6 months of follow-up , mean ( + /- SD ) asthma and pediatric quality -of-life scores were higher in the enhanced care group than in the usual care group ( 5.7 + /- 1.2 units vs. 5.0 + /- 1.3 units , P = 0.01 ) . The enhanced care group also had a higher rate of follow-up office visits ( 78 % [ n = 44 ] vs. 60 % [ n = 33 ] , P = 0.003 ) , were more likely to have written action plans ( 46 % [ n = 26 ] vs. 25 % [ n = 14 ] , P = 0.02 ) , and had fewer asthma symptoms ( 1.8 + /- 1.1 units vs. 2.2 + /- 1.3 units , P = 0.09 ) . However , these differences disappeared by 12 months of follow-up . CONCLUSION A simple intervention wherein a health professional facilitates follow-up visits can improve the process of care and health outcomes of high-risk asthmatic patients . However , the effect of this intervention is time limited and largely wears off by 12 months Background Chronic illness is a significant driver of the global burden of disease and associated health care costs . People living with severe chronic illness are heavy users of acute hospital services ; better coordination of their care could potentially improve health outcomes while reducing hospital use . The Care Navigation trial will evaluate an in-hospital coordinated care intervention on health service use and quality of life in chronically ill patients . Methods / Design A r and omised controlled trial in 500 chronically ill patients presenting to the emergency department of a hospital in Western Sydney , Australia . Participants have three or more hospital admissions within a previous 12 month period and either aged ≥70 years ; or aged ≥45 years and of Aboriginal or Torres Strait Isl and er descent ; or aged ≥ 16 with a diagnosis of a respiratory or cardiology related illness . Patients are r and omised to either the coordinated care program ( Care Navigation ) , or to usual care . The Care Navigation program consists of dedicated nurses who conduct patient risk assessment s , oversee patient nursing while in hospital , and guide development of a care plan for the management of chronic illness after being discharged from hospital . These nurses also book community appointments and liaise with general practitioners . The main outcome variables are the number of emergency department re-presentations and hospital readmissions , and quality of life during a 24 month follow-up . Secondary outcomes are length of hospital stay , mortality , time to first hospital re-admission , time to first emergency department re-presentation , patient satisfaction , adherence to prescribed medications , amount and type of in-hospital referrals made for consultations and diagnostic testing , and the number and type of community health referrals . A process evaluation and economic analysis will be conducted alongside the r and omised trial . Discussion A trial of in-hospital care coordination may support recent evidence that engaging primary health services in care plans linked to multidisciplinary team support improves patient outcomes and reduces costs to the health system . This will inform local , national and international health policy . Trial registration Australia New Zeal and Clinical Trials Registry OBJECTIVES To test the hypothesis that reinforcement of the advice given at the time of discharge from the emergency department by telephone consultation would improve asthma outcomes . METHODS A r and omized controlled trial of the parents of 310 children who had been discharged from the emergency department with asthma was undertaken . The parents were r and omized to receive either st and ard care ( 155 children ) or st and ard care plus education by telephone ( 155 children ) from a trained asthma educator . Symptoms , parental asthma knowledge , parental quality of life and use of asthma action plans and preventer therapy were collected at baseline and 6 months later . The primary measure was days of wheeze in last 3 months ; intermediate measures were regular use of preventer medications , possession and use of written asthma action plan , parental asthma knowledge scores and parental quality of life scores . RESULTS A total of 266 parents ( 136 intervention ) completed the follow-up question naires after 6 months . Both groups showed similar symptoms and process measures at baseline , apart from more regular use of preventer medication in the control children . At follow up , the intervention group children were significantly more likely than controls to possess ( 87.5 % vs 72.3 % ; P = 0.002 ) a written asthma action plan . Possession of action plans increased from baseline in the intervention group but tended to decrease in the control group . Use of action plans was greater in the intervention group but decreased from baseline in both groups . Both intervention and control groups showed significant decreases in asthma symptoms . CONCLUSIONS Reinforcement by telephone consultation did not improve the primary outcome of wheeze in the last 3 months . However , it increased the possession and regular use of written asthma action plans in the intervention group Care of asthmatic children is often episodic and more therapeutic than preventive . A 2-year r and omized , controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures . Interventions for the study group during the first year included 3-month clinic visits , education , and home visits by a specially trained research nurse . Control subjects continued to receive regular care from a family physician or pediatrician . Eight-nine subjects ( 93 % ) completed the study . Study subjects had less school absenteeism than control subjects ( 10.7 vs. 16.0 days , P = .04 ) and showed significantly better small airway function after 1 year . Asthma severity improved in 13 study subjects and worsened in 5 . The reverse was true for control subjects . Study subjects exhibited better metered aerosol technique than control subjects ( P = .0005 ) . Fewer days were spent in hospital by the study subjects admitted compared with control subjects ( 3.67 vs 11.2 days , P = .02 ) . After 1 year , more study than control families ( 72.1 % vs 33.1 % , P = .006 ) reported that their asthmatic child took responsibility for the asthma management . The intervention failed to reduce exposure to secondh and smoke or to household pets . There were no significant differences in medical visits , theophylline levels , or records of asthma symptoms . One year after discontinuing the intervention , a marked " washout " effect was observed . Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained A r and omised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses . Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma . The intervention group was visited monthly by a nurse for six months . The subjects were assessed six months later by a postal , self administered question naire . European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group ( mean ( SD ) intake 2.7 ( 1.1 ) v 2.1 ( 1.0 ) , respectively ) . In particular , they were using more theophylline ( 56.6 % v 37.0 % ) and inhaled steroids ( 34.9 % v 21.0 % ) . There was no difference between the groups for parental reports of improvement , of missed schooling , and in severe attacks of asthma of not responding to the usual treatment at home . European children in the intervention group used the hospital services for severe attacks of asthma more than controls ( 34.2 % v 10.5 % ) . There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group ( mean ( SD ) 0.51 ( 0.97 ) v 0.29 ( 0.65 ) . Re-admission continued to be higher in the 12 months after the nurse had stopped visiting ( 0.81 ( 1.65 ) v 0.25 ( 0.65 ] . There was no difference in the duration of hospital stay between the intervention and control groups . For Polynesian children there was no difference between the groups for any outcome measures Effective self-management and treatment compliance is important in achieving good symptom control in asthma . The aim of this study was to determine whether asthma nurse intervention during hospital admission could increase knowledge and improve self-management and whether this would influence the number of emergency call-out visits by Genera Practitioners ( GPs ) and hospital re-admissions . Patients with acute asthma ( n=80 ) were assessed by the asthma nurse within 24 h of admission using a British Thoracic Society ( BTS ) guideline -based question naire . Main outcome measures were : know edge of inhalers , self-management plans , peak flow monitoring , recognition of worsening symptoms and appropriate emergency action , Following r and omization , half received nurse intervention during hospitalization . All received a follow-up question naire 6 weeks post-discharge and again at 6 months ( response rates 86 % and 81 % respectively ) . GPs were contacted by postal question naire after 4 months . Question naire responses indicated an increase in knowledge in the intervention group , along with an ability to identify appropriate action on worsening symptoms . Emergency GP call-outs were more frequent in the control group in the 4 months post-discharge . Hospital re-admission rates were similar in both groups . Asthma nurse intervention appeared to increase knowledge of asthma management , maintained throughout the study period , but had no significant impact on reducing re-admissions to hospital BACKGROUND Re-admissions to hospital in childhood asthma are common with studies reporting that 25 % or more of children will be re-admitted within a year . There is a need for strategies to reduce re-admissions . METHODS A prospect i ve r and omised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma . Two hundred and one children were r and omised at admission to either an intervention group ( n = 96 ) which received the teaching programme or a control group ( n = 105 ) . A nurse-led teaching programme used the current attack as a model for the management of future attacks and included discussion , written information , subsequent follow up and telephone advice aim ed at developing and reinforcing individualised asthma management plans . Parents were also provided with a course of oral steroids and guidance on when to start them . RESULTS The groups were similar in degree of social deprivation , length of stay , number of previous admissions , acute asthma treatment , and asthma treatment at discharge . Subsequent re-admissions were significantly reduced in the intervention group from 25 % to 8 % in individual follow up periods that ranged from two to 14 months ( chi 2 = 9.63 ; p = 0.002 ) . This reduction was not accompanied by any increase in subsequent emergency room attendances nor , in the short term , by any increase in urgent community asthma treatment . The intervention group also showed significant reductions in day and night morbidity 3 - 4 weeks after admission to hospital . CONCLUSIONS A nurse-led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma . Acute hospitalisation may be a particularly effective time to deliver home management training Background Tanzania has been a pioneer in establishing community-level services , yet challenges remain in sustaining these systems and ensuring adequate human re source strategies . In particular , the added value of a cadre of professional community health workers is under debate . While Tanzania has the highest density of primary health care facilities in Africa , equitable access and quality of care remain a challenge . Utilization for many services proven to reduce child and maternal mortality is unacceptably low . Tanzanian policy initiatives have sought to address these problems by proposing expansion of community-based providers , but the Ministry of Health and Social Welfare ( MoHSW ) lacks evidence that this merits national implementation . The Tanzania Connect Project is a r and omized cluster trial located in three rural districts with a population of roughly 360,000 ( Kilombero , Rufiji , and Ulanga).Description of interventionConnect aims to test whether introducing a community health worker into a general program of health systems strengthening and referral improvement will reduce child mortality , improve access to services , exp and utilization , and alter reproductive , maternal , newborn and child health seeking behavior ; thereby accelerating progress towards Millennium Development Goals 4 and 5 . Connect has introduced a new cadre — Community Health Agents ( CHA ) — who were recruited from and work in their communities . To support the CHA , Connect developed supervisory systems , launched information and monitoring operations , and implemented logistics support for integration with existing district and village operations . In addition , Connect ’s district-wide emergency referral strengthening intervention includes clinical and operational improvements . Evaluation design Design ed as a community-based cluster-r and omized trial , CHA were r and omly assigned to 50 of the 101 villages within the Health and Demographic Surveillance System ( HDSS ) in the three study districts . To garner detailed information on household characteristics , behaviors , and service exposure , a r and om sub- sample survey of 3,300 women of reproductive age will be conducted at the baseline and endline . The referral system intervention will use baseline , midline , and endline facility-based data to assess systemic changes . Implementation and impact research of Connect will assess whether and how the presence of the CHA at village level provides added life-saving value to the health system . Discussion Global commitment to launching community-based primary health care has accelerated in recent years , with much of the implementation focused on Africa . Despite extensive investment , no program has been guided by a truly experimental study . Connect will not only address Tanzania ’s need for policy and operational research , it will bridge a critical international knowledge gap concerning the added value of salaried professional community health workers in the context of a high density of fixed facilities . Trial registration : IS RCT Objective . To compare three pediatric asthma interventions for their impact on improving the health status of inner-city asthmatic children and in achieving cost savings . Study Design . A total of 212 children 1 to 16 years of age were r and omized into three groups : group 1 ( n = 74 ) received one individualized asthma education session ; group 2 ( n = 68 ) received reinforced asthma education ; group 3 ( n = 70 ) received reinforced asthma education plus case management . Asthma-related health re source utilization and cost were primary outcomes . The cost-benefit analysis sought to estimate the expected cost savings to the Illinois Department of Healthcare and Family Services ( Medicaid administrator ) associated with the intervention . Results . Participants in all three groups used significantly fewer emergency health care services in the follow-up year . Averaged across all three groups , the magnitudes of declines were substantial : 81 % for hospitalizations , 69 % for hospital days , 64 % for emergency department visits , and 58 % for clinic visits . Although there were no statistically significant differences between study groups for three of the four main outcome measures , group 3 participants consistently improved to the greatest degree . All three interventions were associated with considerable cost savings ranging from $ 4,021/child/year for group 1 to $ 4,503/child/year for group 3 . Conclusion . Asthma education with or without case management services enhances the health of children with asthma thereby reducing associated costs BACKGROUND Asthma is common and is often poorly controlled in adolescent subjects . OBJECTIVE To determine the impact of an age-specific asthma program on asthma control , particularly on exacerbations of asthma requiring emergency department treatment , and on the quality of life of adolescents with asthma . METHODS The present r and omized , controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma . The interventional group attended an age-specific asthma program that included assessment , education and management by a team of asthma educators , respiratory therapists and respiratory physicians . In the control group , spirometry was performed , and the patients continued to receive usual care from their regular physicians . The outcomes were assessed by a question naire six months after entry into the study . RESULTS Ninety-three subjects entered the study and were r and omly assigned to the intervention or control group . Of these , only 62 patients were available for review after six months . Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control , reflected primarily by a 73 % reduction in the rate of emergency department attendance for asthma . Other indexes of disease control , including disease-specific quality of life , as assessed by question naires , were improved . There was , however , no discernible difference between the subjects in the two groups , with the exception of an improvement in favour of the intervention group in the symptom ( actual difference 0.7 , P=0.048 ) and emotional ( actual difference 0.8 , P=0.028 ) domains of the asthma quality of life question naire . The overall quality of life score favoured the intervention group by a clinical ly relevant difference of 0.6 , but this difference did not reach statistical significance ( P=0.06 ) . CONCLUSIONS Although all subjects demonstrated a significant improvement in asthma control and quality of life , the improvement attributable to this intervention was limited to two domains in disease-specific quality of life OBJECTIVE . We sought to study the impact of emergency department (ED)–based intensive primary care linkage and initiation of asthma case management on long-term , patient-oriented outcomes for children with an asthma exacerbation . METHODS . Our study was a r and omized , 3-arm , parallel-group , single-blind clinical trial . Children aged 2 through 17 years treated in a pediatric ED for acute asthma were r and omly assigned to st and ard care ( group 1 ) , including patient education , a written care plan , and instructions to follow up with the primary care provider within 7 days , or 1 of 2 interventions . Group 2 received st and ard care plus assistance with scheduling follow-up , while group 3 received the above interventions , plus enrollment in a case management program . OUTCOMES . The primary outcome was the proportion of children having an ED visit for asthma within 6 months . Other outcomes included change in quality -of-life score and controller-medication use . RESULTS . Three hundred fifty-two children were enrolled ; 78 % completed follow-up , 69 % were black , and 70 % had persistent asthma . Of the children , 37.8 % had a subsequent ED visit for asthma , with no difference among the treatment groups ( group 1 : 38.4 % ; group 2 , 39.2 % ; group 3 , 35.8 % ) . Children in all groups had a substantial , but similar , increase in their quality -of-life score . Controller-medication use increased from 69.4 % to 81.4 % , with no difference among the groups . CONCLUSION . ED-based attempts to improve primary care linkage or initiate case management are no more effective than our st and ard ED care in improving subsequent asthma outcomes over a 6-month period OBJECTIVE To evaluate the efficacy of a comprehensive asthma program on emergency department ( ED ) visits and hospital admission rates in an inner-city pediatric population . DESIGN A12-month prospect i ve r and omized trial . METHODS Three hundred asthma patients , ages 2 to 17 years , were recruited and r and omized in an inner-city pediatric ED , to obtain asthma care in a specialty clinic or to continue receiving care by other health re sources . The specialty clinic provided intensive medical and environmental control , education , close monitoring , and 24-hour availability . For the prospect i ve study , monthly question naires were sent to the caregivers of these children to evaluate use of hospital facilities for asthma care . For the retrospective study , use of hospital re sources by the study participants was analyzed using a hospital data base . RESULTS One hundred twenty-nine patients ( 60 in the treatment group and 69 in the control group ) were included in the final analysis . Asthma severity index was significantly higher for the patients in the treatment versus the control group ( 35 % versus 16.2 % , P = .05 ) . Fewer patients in the treatment group visited the ED at least once during the first study year , 32 versus 46 , ( P = .11 ) , and they made fewer visits , 73 versus 269 . The mean number of ED visits of the patients who used the ED was 0.1 versus 0.326 for the control group ( P = .01 ) . There were also fewer admissions in the treatment group , 22 versus 29 ( P < .59 ) . The 53 patients remaining in the treatment group in the second study year made fewer visits to the ED versus the control group ( P < .03 ) . In comparison to the first year , fewer patients in the treatment group visited the ED or were hospitalized in the second year ( P = .007 and P = .04 , respectively ) . CONCLUSIONS A comprehensive asthma care program is efficacious in reducing hospital utilization A clinic supervised by a nurse , using principles originally developed in general practice , was established in the paediatric department of a district general hospital . A r and omised controlled study was conducted comparing children admitted with asthma or attending out patients who were given a patient education programme and self management plan ( intervention group ) with a control group . The study comprised 91 patients aged 3 - 14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990 . Seventy seven patients completed the study and kept diaries for a median of 283 days . Patients in the intervention group had significantly less restriction of activity ( 95 % confidence interval ( CI ) -0.27 to -0.01 ) and fewer episodes of peak flow below 30 % of best ( 95 % CI 0.03 to 1.17 ) . Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group ( 71 % v 47 % , 95 % CI 9.51 to 39.1 ) . The intervention group had fewer school absences and fewer home visits by a general practitioner . There was an increase in the readmission rate for the intervention group . A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone . Improvements in patient follow up and the structure of the self management plans used , particularly changing the peak flow level at which inhaled steroids are doubled , may further improve the outcome of patients attending the asthma clinic 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 ) Objective To determine whether asthma specialist nurses , using a liaison model of care , reduce unscheduled care in a deprived multiethnic area . Design Cluster r and omised controlled trial . Setting 44 general practice s in two boroughs in east London . Participants 324 people aged 4 - 60 years admitted to or attending hospital or the general practitioner out of hours service with acute asthma ; 164 ( 50 % ) were South Asian patients , 108 ( 34 % ) were white patients , and 52 ( 16 % ) were from other , largely African and Afro-Caribbean , ethnicities . Intervention Patient review in a nurse led clinic and liaison with general practitioners and practice nurses comprising educational outreach , promotion of guidelines for high risk asthma , and ongoing clinical support . Control practice s received a visit promoting st and ard asthma guidelines ; control patients were checked for inhaler technique . Main outcome measures Percentage of participants receiving unscheduled care for acute asthma over one year and time to first unscheduled attendance . Results Primary outcome data were available for 319 of 324 ( 98 % ) participants . Intervention delayed time to first attendance with acute asthma ( hazard ratio 0.73 , 95 % confidence interval 0.54 to 1.00 ; median 194 days for intervention and 126 days for control ) and reduced the percentage of participants attending with acute asthma ( 58 % ( 101/174 ) v 68 % ( 99/145 ) ; odds ratio 0.62 , 0.38 to 1.01 ) . In analyses of prespecified subgroups the difference in effect on ethnic groups was not significant , but results were consistent with greater benefit for white patients than for South Asian patients or those from other ethnic groups . Conclusion Asthma specialist nurses using a liaison model of care reduced unscheduled care for asthma in a deprived multiethnic health district . Ethnic groups may not benefit equally from specialist nurse intervention OBJECTIVE To study the effect of an asthma outreach program on emergency ward and hospital utilization . DESIGN Before and after trial . SETTING Ambulatory patients in a staff-model health maintenance organization with a 70 % black inner-city population . PATIENTS Fifty-three patients aged 1 to 17 years with the diagnosis of asthma based on usual clinical practice criteria . INTERVENTION Asthma emergency ward visits and hospitalizations were monitored over a 6-month to 2-year period after enrollment in the program . Patients were scheduled for one-on-one orientation visits with the asthma outreach nurse and instructed in asthma management , medications , triggers , and use of inhalers and peak flowmeters . An individualized step-care treatment program was outlined for each patient by the nurse , primary care pediatrician , and , when appropriate , an allergist . The outreach nurse maintained personal or telephone contact with the families on a regular basis to assure underst and ing of and compliance with the treatment plan . OUTCOME MEASURES Outcome was assessed by measuring annualized emergency ward and hospital admissions for each patient for an equal period before and after entry into the program . RESULTS Emergency ward admissions were reduced 79 % ( from a rate of 72 visits per year to 15 visits per year , P < .0001 ) and hospital admissions were reduced 86 % ( from 35 per year to five per year , P < .001 ) . These reductions were achieved by a single outreach nurse working an average of 8 hours per week at an annualized cost of $ 11,115 ; this saved approximately $ 87,000 in costs . CONCLUSIONS Patients enrolled in a pediatric asthma outreach program experienced a significant reduction in utilization of emergency ward and hospital admissions , result ing in reduced cost of care OBJECTIVE To compare the marginal benefit of in-home asthma self-management support provided by community health workers ( CHWs ) with st and ard asthma education from clinic-based nurses . DESIGN R and omized controlled trial . SETTING Community and public health clinics and homes . PARTICIPANTS Three hundred nine children aged 3 to 13 years with asthma living in low-income households . INTERVENTIONS All participants received nurse-provided asthma education and referrals to community re sources . Some participants also received CHW-provided home environmental assessment s , asthma education , social support , and asthma-control re sources . OUTCOME MEASURES Asthma symptom-free days , Pediatric Asthma Caretaker Quality of Life Scale score , and use of urgent health services . RESULTS Both groups showed significant increases in caretaker quality of life ( nurse-only group : 0.4 points ; 95 % confidence interval [ CI ] , 0.3 - 0.6 ; nurse + CHW group : 0.6 points ; 95 % CI , 0.4 - 0.8 ) and number of symptom-free days ( nurse only : 1.3 days ; 95 % CI , 0.5 - 2.1 ; nurse + CHW : 1.9 days ; 95 % CI , 1.1 - 2.8 ) , and absolute decreases in the proportion of children who used urgent health services in the prior 3 months ( nurse only : 17.6 % ; 95 % CI , 8.1%-27.2 % ; nurse + CHW : 23.1 % ; 95 % CI , 13.6%-32.6 % ) . Quality of life improved by 0.22 more points in the nurse + CHW group ( 95 % CI , 0.00 - 0.44 ; P = .049 ) . The number of symptom-free days increased by 0.94 days per 2 weeks ( 95 % CI , 0.02 - 1.86 ; P = .046 ) , or 24.4 days per year , in the nurse + CHW group . While use of urgent health services decreased more in the nurse + CHW group , the difference between groups was not significant . CONCLUSION The addition of CHW home visits to clinic-based asthma education yielded a clinical ly important increase in symptom-free days and a modest improvement in caretaker quality of life BACKGROUND Acute respiratory exacerbations ( AREs ) cause morbidity and lung function decline in children with chronic suppurative lung disease ( CSLD ) and bronchiectasis . In a prospect i ve longitudinal cohort study , we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis . METHODS Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia ( n = 57 ) and Alaska ( n = 36 ) during 2004 to 2009 were followed for > 3 years . St and ardized parent interviews , physical examinations , and medical record review s were undertaken at enrollment and every 3 to 6 months thereafter . RESULTS Ninety-three children experienced 280 AREs ( median = 2 , range = 0 - 11 per child ) during the 3-year period ; 91 ( 32 % ) were associated with pneumonia , and 43 ( 15 % ) result ed in hospitalization . Of the 93 children , 69 ( 74 % ) experienced more than two AREs over the 3-year period , and 28 ( 30 % ) had more than one ARE in each study year . The frequency of AREs declined significantly over each year of follow-up . Factors associated with recurrent ( two or more ) AREs included age < 3 years , ARE-related hospitalization in the first year of life , and pneumonia or hospitalization for ARE in the year preceding enrollment . Factors associated with hospitalizations for AREs in the first year of study included age < 3 years , female caregiver education , and regular use of bronchodilators . CONCLUSIONS AREs are common in children with CSLD/bronchiectasis , but with clinical care and time AREs occur less frequently . All children with CSLD/bronchiectasis require comprehensive care ; however , treatment strategies may differ for these patients based on their changing risks for AREs during each year of care BACKGROUND Discharge planning is becoming an important part of the management of childhood asthma in hospital . Readmission to hospital , although often inevitable , might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital . AIM To examine the impact of a structured , nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital , reattendance at the accident and emergency ( A&E ) department , and general practitioner consultations for asthma . METHODS A structured nurse-led discharge package , consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children ’s hospital . A r and omised controlled trial was conducted involving 160 children aged 2–16 years admitted for asthma over a 12 month period . Readmission and A&E reattendance ’s over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records . RESULTS Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group ( 12 of 80 v30 of 80 patients ) , and significantly less likely to attend the A&E department ( 6 of 80 v 31 of 80 ) . Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma ( 31 of 78v 72 of 77 for whom data were available ) . CONCLUSION By delivering the simplest form of education and support during a child ’s stay in hospital , readmissions over a six month period were reduced . The programme was design ed to be suitable for administration by nursing staff on the children ’s wards after a brief period of training BACKGROUND Previous studies have shown that asthma education and case management may reduce asthma emergency care , hospitalizations , and expenditures . OBJECTIVE We sought to study the effect of an asthma outreach program ( AOP ) , a team-based , case-management intervention , on emergency ward ( EW ) and hospital use . METHODS Fifty-seven patients aged 1 to 15 years with the diagnosis of asthma based on the usual clinical practice criteria who were continuously enrolled in a staff-model health maintenance organization for a period of at least 2 consecutive years were r and omized into 2 intervention groups . The control group received a single intensive asthma education intervention , and the AOP group received the same initial education but then was followed-up by an asthma case management nurse throughout the intervention period . RESULTS EW visits , hospitalizations , and total outside-of-health-plan expenditures ( consisting of EW and hospital expenses , as well as miscellaneous costs , such as ambulance , durable medical equipment , tertiary referrals , and home care ) were assessed from cl aims filed for a year before and after enrollment . Control group patients experienced significant reductions in EW visits ( 39 % ) , hospitalizations ( 43 % ) , and outside-of-health-plan costs ( 28 % ) , possibly as a result of the baseline educational intervention received by all enrolled patients , in conjunction with regression to the mean . AOP group patients experienced significant reductions in EW visits , ( 73 % , P = .0002 ) , hospitalizations ( 84 % , P = .0012 ) , and outside-of-health-plan use ( 82 % , P < .0001 ) . When compared with the control group , AOP group patients demonstrated additional significant reductions in EW visits ( 57 % , P < .05 ) , hospitalizations ( 75 % , P < .05 ) , and outside-of-health-plan use ( 71 % , P < .001 ) . Estimates of direct savings to the health plan ranged from $ 7.69 to $ 11.67 for every dollar spent on the AOP nurse 's salary , depending on assumptions . CONCLUSIONS Asthma patients in a staff-model health maintenance organization decreased their re source use between 57 % to 75 % by participation in an AOP as compared with a r and omized control group receiving only an educational intervention . Substantial savings were achieved compared with the cost of the AOP nurse OBJECTIVE To assess whether efforts to actively involve General Practitioners ( GPs ) in the postdischarge care of their paediatric asthma patients improved their satisfaction with communication with hospital staff . METHODOLOGY R and omized controlled trial involving 60 patients admitted to the Royal Children 's Hospital , Melbourne , with acute asthma and an identifiable GP . The GPs of the intervention patients were telephoned during the admission . Intervention patients and their GPs received printed information detailing the care the patient received in hospital and the recommended postdischarge care , as well as st and ardized educational booklets about asthma . Follow-up appointments were made for intervention patients to attend their GPs . RESULTS The GPs of intervention patients were more satisfied when compared to the GPs receiving a st and ard level of communication ( 96.4 % vs 48.3 % of the intervention and control GPs , respectively , described the communication as good or extremely good , P = 0.0001 ) . The intervention group GPs believed they were more involved after discharge ( 75.0 % vs 44.8 % , P = 0.005 ) and had greater underst and ing of their patient 's hospitalisation ( 96.4 % vs 62.1 % , P = 0.005 ) . These differences were noted despite there being no difference in the rate of follow-up attendance with GPs for intervention and control patients ( 85.7 % vs 72.4 % , P = 0.2 ) . Qualitative data supported these findings with GPs expressing approval of the intervention used . CONCLUSION Efforts to actively involve GPs in the postdischarge care of their paediatric patients with asthma result ed in a marked improvement in their satisfaction with the communication with medical staff at the Royal Children 's Hospital , Melbourne . The study had insufficient power to demonstrate a difference in morbidity OBJECTIVE To evaluate the impact of LEAP , a volunteer-based , inpatient asthma education program for families of inner-city children with asthma . METHODS 711 children ages 2 - 17 years admitted with status asthmaticus were r and omized to receive usual care or usual care plus a supplemental education intervention . Both groups completed a baseline interview . Trained volunteer lay educators conducted individualized bedside education with the intervention group . Primary outcome was attendance at a post-hospitalization follow-up visit 7 - 10 days after discharge . Secondary outcomes included parent-reported asthma management behaviors , symptoms , and self-efficacy scores from a one month follow-up interview . RESULTS Post-hospitalization asthma clinic attendance was poor ( 38 % ) , with no difference between groups . Families r and omized to the intervention group were more likely to report use of a controller ( OR 2.4 , 95 % CI 1.3 - 4.2 , p<0.01 ) and a valved-holding chamber ( OR 2.9 , 95 % CI 1.1 - 7.4 , p=0.03 ) , and were more likely to have an asthma action plan at follow up ( OR 2.0 , 95 % CI 1.3 - 3.0 , p<0.01 ) . Asthma self-efficacy scores were significantly improved among those who received the intervention ( p=0.04 ) . CONCLUSIONS Inpatient asthma education by trained lay volunteers was associated with improved asthma management behaviors . PRACTICE IMPLICATION S This novel volunteer-based program could have widespread implication s as a sustainable model for asthma education Objective Previous studies demonstrate that patients often have difficulty underst and ing their discharge instructions . Video discharge instructions have the potential to mitigate factors such as illiteracy and limited physician time , which may affect comprehension . Our goal is to determine if adding video discharge instructions affects caregivers ’ underst and ing of their child ’s emergency department ( ED ) visit , plan , and follow-up . Methods Caregivers of patients , aged 29 days to 18 years , with a diagnosis of fever , vomiting or diarrhea , and wheezing or asthma were r and omized into written or video discharge instruction groups . In the ED , caregivers read st and ard written discharge instructions or watched a 3-minute video based on their child ’s diagnosis . They were then asked questions regarding information covered in these instructions . After completing the 20-point question naire , st and ard discharge procedure was followed . Caregivers were contacted by phone 2 to 5 days after discharge for a follow-up question naire . Usefulness of the discharge instructions was also assessed . Results Of 436 caregivers enrolled , 220 received written and 216 received video discharge instructions . The follow-up question naire was completed by 341 caregivers . The group receiving video discharge instructions scored significantly higher in the ED ( 12.2 vs 8.9 ) and 2 to 5 days after discharge ( 11.1 vs 7.8 ) . At follow-up , 29 % of the written and 42 % of the video groups rated their discharge instructions as being extremely helpful . Conclusions Brief video discharge instructions improved caregiver knowledge both in the ED and 2 to 5 days after discharge compared with written discharge instructions alone . Caregiver satisfaction with video discharge instructions was also greater than with written discharge instructions |
499 | 30,808,419 | Conclusion YLWHA experience numerous challenges and support needs , some of which occur in schools and affect their QoL. The effects of these challenges are poor health and educational outcomes as well as school dropout .
The schools in which youths spend most of their formative years have not provided adequate support for YLWHA . | Background Youths living with HIV/AIDS ( YLWHA ) experience innumerable challenges within schools and the larger community .
Nonetheless , these environments are potential sources of support for such youths .
This review provides a synthesis of evidence about these challenges and support available for YLWHA to inform the design and implementation of interventions that support the wellbeing of youths living with HIV/AIDS in an East African context . | Introduction A better underst and ing of pediatric antiretroviral therapy ( ART ) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence . Methodology /Principal Findings Adherence among 96 HIV-infected Zambian children ( median age 6 , interquartile range [ IQR ] 2,9 ) initiating fixed-dose combination ART was measured prospect ively ( median 23 months ; IQR 20,26 ) with caregiver report , clinic and unannounced home-based pill counts , and medication event monitoring systems ( MEMS ) . HIV-1 RNA was determined at 48 weeks . Child and caregiver characteristics , socio-demographic status , and treatment-related factors were assessed as predictors of adherence . Median adherence was 97.4 % ( IQR 96.1,98.4 % ) by visual analog scale , 94.8 % ( IQR 86,100 % ) by caregiver-reported last missed dose , 96.9 % ( IQR 94.5,98.2 % ) by clinic pill count , 93.4 % ( IQR 90.2,96.7 % ) by unannounced home-based pill count , and 94.8 % ( IQR 87.8,97.7 % ) by MEMS . At 48 weeks , 72.6 % of children had HIV-1 RNA < 50 copies/ml . Agreement among adherence measures was poor ; only MEMS was significantly associated with viral suppression ( p = 0.013 ) . Predictors of poor adherence included changing residence , school attendance , lack of HIV disclosure to children aged nine to 15 years , and increasing household income . Conclusions / Significance Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years . However , certain groups are at risk for treatment failure , including children with disrupted routines , no knowledge of their HIV diagnosis among older children , and relatively high household income , possibly reflecting greater social support in the setting of greater poverty Background For youth living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome ( AIDS ) , nonadherence to antiretroviral therapy ( ART ) can lead to poor health outcomes and significantly decreased life expectancy . Objective To evaluate the feasability , acceptability , and preliminary efficacy of short message service ( SMS ) or text message reminders to improve adherence to ART for youth living with HIV/AIDS . Methods We conducted this prospect i ve pilot study using a pre – post design from 2009 to 2010 at a community-based health center providing clinical services to youth living with HIV/AIDS . Eligibility criteria included HIV-positive serostatus , age 14–29 years , use of a personal cell phone , English-speaking , and being on ART with documented poor adherence . During the 24-week study period , participants received personalized daily SMS reminders and a follow-up message 1 hour later assessing whether they took the medication , and asking participants to respond via text message with the number 1 if they took the medication and 2 if they did not . Outcome measures were feasibility , acceptability , and adherence . Self-reported adherence was determined using the visual analog scale ( VAS ) and AIDS Clinical Trial Group ( ACTG ) question naire 4-day recall . Viral load and CD4 cell count were followed as biomarkers of adherence and disease progression at 0 , 12 , and 24 weeks . Results Participants ( N = 25 ) were mean age 23 ( range 14–29 ) years , 92 % ( n = 23 ) male , 60 % ( n = 15 ) black , and 84 % ( n = 21 ) infected through unprotected sex . Mean VAS scores significantly increased at 12 and 24 weeks in comparison with baseline ( week 0 : 74.7 , week 12 : 93.3 , P < .001 ; week 24 : 93.1 , P < .001 ) . ACTG question naire 4-day recall also improved ( week 0 : 2.33 , week 12 : 3.24 , P = .002 ; week 24 : 3.19 , P = .005 ) . There was no significant difference in CD4 cell count or viral load between baseline and 12- or 24-week follow-up , although there was a trend toward improvement of these biomarkers and a small to moderate st and ardized effect size ( range of Cohen d : –0.51 to 0.22 ) . Of 25 participants , 21 ( 84 % ) were retained , and 20 of the 21 ( 95 % ) participants who completed the study found the intervention helpful to avoid missing doses . Conclusions In this pilot study , personalized , interactive , daily SMS reminders were feasible and acceptable , and they significantly improved self-reported adherence . Larger controlled studies are needed to determine the impact of this intervention on ART adherence and other related health outcomes for youth living with HIV/AIDS CONTEXT Physical activity has been shown to decrease the incidence of breast cancer , but the effect on recurrence or survival after a breast cancer diagnosis is not known . OBJECTIVE To determine whether physical activity among women with breast cancer decreases their risk of death from breast cancer compared with more sedentary women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study based on responses from 2987 female registered nurses in the Nurses ' Health Study who were diagnosed with stage I , II , or III breast cancer between 1984 and 1998 and who were followed up until death or June 2002 , whichever came first . MAIN OUTCOME MEASURE Breast cancer mortality risk according to physical activity category ( <3 , 3 - 8.9 , 9 - 14.9 , 15 - 23.9 , or > or = 24 metabolic equivalent task [ MET ] hours per week ) . RESULTS Compared with women who engaged in less than 3 MET-hours per week of physical activity , the adjusted relative risk ( RR ) of death from breast cancer was 0.80 ( 95 % confidence interval [ CI ] , 0.60 - 1.06 ) for 3 to 8.9 MET-hours per week ; 0.50 ( 95 % CI , 0.31 - 0.82 ) for 9 to 14.9 MET-hours per week ; 0.56 ( 95 % CI , 0.38 - 0.84 ) for 15 to 23.9 MET-hours per week ; and 0.60 ( 95 % CI , 0.40 - 0.89 ) for 24 or more MET-hours per week ( P for trend = .004 ) . Three MET-hours is equivalent to walking at average pace of 2 to 2.9 mph for 1 hour . The benefit of physical activity was particularly apparent among women with hormone-responsive tumors . The RR of breast cancer death for women with hormone-responsive tumors who engaged in 9 or more MET-hours per week of activity compared with women with hormone-responsive tumors who engaged in less than 9 MET-hours per week was 0.50 ( 95 % CI , 0.34 - 0.74 ) . Compared with women who engaged in less than 3 MET-hours per week of activity , the absolute unadjusted mortality risk reduction was 6 % at 10 years for women who engaged in 9 or more MET-hours per week . CONCLUSIONS Physical activity after a breast cancer diagnosis may reduce the risk of death from this disease . The greatest benefit occurred in women who performed the equivalent of walking 3 to 5 hours per week at an average pace , with little evidence of a correlation between increased benefit and greater energy expenditure . Women with breast cancer who follow US physical activity recommendations may improve their survival Background Mobile phone technology is a novel way of delivering health care and improving health outcomes . This trial investigates the use of motivational mobile phone text messages ( SMS ) to improve adherence to antiretroviral therapy ( ART ) over six months . Methodology /Principal Findings CAMPS was a single-site r and omized two-arm parallel design trial in Yaoundé , Cameroon . We enrolled and r and omized HIV-positive adults on ART , aged 21 years and above to receive a weekly st and ardized motivational text message versus usual care alone . The primary outcome was adherence measured using a visual analogue scale ( VAS ) , number of doses missed ( in the week preceding the interview ) and pharmacy refill data . Outcomes were measured at 3 and 6 months . Service providers and outcome assessors were blinded to allocation . Analysis was by intention-to-treat . Between November and December 2010 , 200 participants were r and omized , with 101 in the intervention group and 99 in the control group . At 6 months , overall retention was 81.5 % . We found no significant effect on adherence by VAS>95 % ( risk ratio [ RR ] 1.06 , 95 % confidence interval [ CI ] 0.89 , 1.29 ; p = 0.542 ; reported missed doses ( RR 1.01 , 95 % CI 0.87 , 1.16 ; p>0.999 ) or number of pharmacy refills ( mean difference [ MD ] 0.1 , 95 % CI : 0.23 , 0.43 ; p = 0.617 . One participant in the intervention arm reported a possible disclosure of status . Conclusions / Significance St and ardized motivational mobile phone text messages did not significantly improve adherence to ART in this study . Other types of messaging or longer term studies are recommended . Registration 1 . Pan-African Clinical Trials Registry ; PACTR201011000261458 2 . Clinical trials.gov ; Background Many HIV-infected children in sub-Saharan Africa reside in rural areas , yet most research on treatment outcomes has been conducted in urban centers . Rural clinics and residents may face unique barriers to care and treatment . Methods A prospect i ve cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha , Zambia . HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy ( ART ) during the study were eligible . Treatment outcomes during the first two years of ART , including mortality , immunologic status , and virologic suppression , were assessed and risk factors for mortality and virologic suppression were evaluated . Results A total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment . The cumulative probabilities of death among children starting ART after study enrollment were 9.0 % and 14.4 % at 6 and 24 months after ART initiation . Younger age , higher viral load , lower CD4 + T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality . The mean CD4 + T-cell percentage increased from 16.3 % at treatment initiation to 29.3 % and 35.0 % at 6 and 24 months . The proportion of children with undetectable viral load increased to 88.5 % and 77.8 % at 6 and 24 months . Children with longer travel times ( ≥5 hours ) and those taking nevirapine at ART initiation , as well as children who were non-adherent , were less likely to achieve virologic suppression after 6 months of ART . Conclusions HIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements . Children with longer travel times were less likely to achieve virologic suppression , supporting the need for de central ized models of ART delivery Introduction With the availability of antiretroviral therapy ( ART ) and primary general care for people living with HIV ( PLHIV ) in re source limited setting s , PLHIV are living longer , and HIV has been transformed into a chronic illness . People are diagnosed and started on treatment when they are relatively well . Although ART results in clinical improvement , the ultimate goal of treatment is full physical functioning and general well-being , with a focus on quality of life rather than clinical outcomes . However , there has been little research on the relationship of specific factors to quality of life in PLHIV . The objective of this study was to investigate factors associated with quality of life among PLHIV in Ug and a receiving basic care and those on ART . Methods We enrolled 1274 patients attending an HIV outpatient clinic into a prospect i ve cohort study . Of these , 640 received ART . All were followed up at 3 and 6 months . Health related quality of life was assessed with the MOS-HIV Health Survey and the Global Person Generated Index ( GPGI ) . Multivariate linear regression and logistic regression with generalized estimating equations were used to examine the relationship of social behavioral and disease factors with Physical Health Summary ( PHS ) score , Mental Health Summary ( MHS ) score , and GPGI . Results Among PLHIV receiving basic care , PHS was associated with : sex ( p=0.045 ) - females had lower PHS ; age in years at enrollment ( p=0.0001 ) - older patients had lower PHS ; and depression ( p<0.001 ) - depressed patients had lower PHS . MHS was only associated with opportunistic infection ( p=0.01 ) - presence of an opportunistic infection was associated with lower MHS . For the GPG the associated variables were age ( p=0.03 ) - older patients had lower GPGI ; education ( p=0.01 ) – higher education associated with higher GPGI ; and depression - patients with depression had a lower GPGI ( p<0.001 ) . Among patients on ART , PHS was associated with : study visit ( p=0.01 ) , with increase in time there was better PHS , and this also improved with increase in education level ( p=0.002 ) . Patients with WHO disease stage 3&4 had a lower PHS compared to patients at stage 1&2 ( p=0.006 ) , and depressed patients had lower PHS ( p<0.001 ) . MHS improved from baseline to six month study visit ( p<0.001 ) , and females had lower MHS compared to males ( p=0.01 ) . GPGI was associated with higher income ( p=0.04 ) , alcohol use was associated with lower GPGI ( p=0.004 ) , and depressed patients had a lower GPGI ( p<0.001 ) . Conclusion Quality of life improved over time for PLHIV on ART . Regardless of treatment status , PLHIV with depression or low education level and female gender were at risk of having a poor quality of life . Clinicians and policy makers should be aware of these findings , and address them to improve quality of life for PLHIV OBJECTIVE This study sought to evaluate the effectiveness of a multidisciplinary elementary school-based intervention entitled Wellness , Academics & You . The primary areas of impact examined were BMI , consumption of fruits and vegetables , and physical activity . RESEARCH METHODS AND PROCEDURES The sample consisted of 1013 students in fourth and fifth grade s from 69 classes in four states . Intervention and comparison classes were r and omly selected at each school . Intervention teachers participated in workshops on the intervention and received program material s. BMI was calculated for baseline and post- data points based on measured height and weight collected by trained research teams . Baseline surveys were administered by the students ' teacher in the presence of one of the research team members and collected . RESULTS SPSS ( SPSS , Inc. , Chicago , IL ) analysis of post- data shows significant positive shifts ( p = 0.01 ) in BMI in the intervention group compared with the comparison group . Notable increases in the consumption of fruits and vegetables and increased physical activity levels were reported in the intervention group . DISCUSSION Data from this study indicate that this school-based program may contribute to the reduction of overweight and obesity . The intervention was well received by the classroom teachers and shows promise for a school-based obesity prevention initiative . This program has shown the capacity to effect positive changes in BMI through consumption of fruits and vegetables and physical activity . The evaluation covered a limited time period and , therefore , warrants additional studies to determine whether long-term program fidelity will result in continued improvement BACKGROUND Mobile ( cell ) phone communication has been suggested as a method to improve delivery of health services . However , data on the effects of mobile health technology on patient outcomes in re source -limited setting s are limited . We aim ed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load . METHODS WelTel Kenya1 was a multisite r and omised clinical trial of HIV-infected adults initiating antiretroviral therapy ( ART ) in three clinics in Kenya . Patients were r and omised ( 1:1 ) by simple r and omisation with a r and om number generating program to a mobile phone short message service ( SMS ) intervention or st and ard care . Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. R and omisation , laboratory assays , and analyses were done by investigators masked to treatment allocation ; however , study participants and clinic staff were not masked to treatment . Primary outcomes were self-reported ART adherence ( > 95 % of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits ) and plasma HIV-1 viral RNA load suppression ( < 400 copies per mL ) at 12 months . The primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , NCT00830622 . FINDINGS Between May , 2007 , and October , 2008 , we r and omly assigned 538 participants to the SMS intervention ( n=273 ) or to st and ard care ( n=265 ) . Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group ( relative risk [ RR ] for non-adherence 0·81 , 95 % CI 0·69 - 0·94 ; p=0·006 ) . Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group , ( RR for virologic failure 0·84 , 95 % CI 0·71 - 0·99 ; p=0·04 ) . The number needed to treat ( NNT ) to achieve greater than 95 % adherence was nine ( 95 % CI 5·0 - 29·5 ) and the NNT to achieve viral load suppression was 11 ( 5·8 - 227·3 ) . INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals . Mobile phones might be effective tools to improve patient outcome in re source -limited setting s. FUNDING US President 's Emergency Plan for AIDS Relief Background : Reductions in AIDS-related morbidity and mortality following the advent of combination antiretroviral therapy have coincided with relative increases in chronic non-AIDS end-organ diseases among HIV+ patients . Objective : To examine the association of latest CD4 + counts with risk of non-AIDS diseases in a cohort of 1397 patients who initiate antiretroviral therapy . Methods : CD4 + counts and HIV RNA levels along with fatal , and non-fatal , AIDS and non-AIDS diseases ( liver , cardiovascular , renal , and cancer ) were assessed over a median follow-up of 5 years . Cox proportional regression models were used to study risk associations . Results : A total of 227 patients experienced an AIDS event and 80 patients developed a non-AIDS disease event . Both AIDS and non-AIDS diseases rates ( events/100 person-years ) , respectively , declined with higher latest CD4 + counts : 13.8 and 2.1 with latest CD4 + counts less than 200 cells/μl ; 2.0 and 1.7 for counts of 200–350 cells/μl ; and 0.7 and 0.7 for counts greater than 350 cells/μl . After adjusting for baseline covariates and the latest HIV RNA level , risk of AIDS and non-AIDS diseases were lowered by 44 % ( 95 % confidence interval for hazard ratio 0.50–0.62 , P < 0.01 ) and 14 % ( 95 % confidence interval for hazard ratio 0.77–0.96 , P = 0.01 ) , respectively , for each 100 cell/μl higher latest CD4 + count . Conclusion : Higher CD4 + counts on antiretroviral therapy are associated with lower rates of non-AIDS diseases and AIDS . These findings exp and our underst and ing of the implication s of HIV-related immunodeficiency and motivate r and omized studies to evaluate the effects of antiretroviral therapy on a broad set of clinical outcomes at CD4 + counts greater than 350 cells/μl Objective : To examine if there is a significant difference in survival between elderly ( > 50 years ) and nonelderly adult patients receiving combination antiretroviral therapy in Ug and a between 2004 and 2010 . Design : Prospect i ve observational study . Methods : Patients 18–49 years of age ( nonelderly ) and 50 years of age and older enrolled in the AIDS Support Organization Ug and a HIV/AIDS national programme were assessed for time to all-cause mortality . We applied a Weibull multivariable regression . Results : Among the 22 087 patients eligible for analyses , 19 657 ( 89.0 % ) were aged between 18 and 49 years and 2430 ( 11.0 % ) were aged 50 years or older . These population s differed in terms of the distributions of sex , baseline CD4 cell count and death . The age group 40–44 displayed the lowest crude mortality rate [ 31.4 deaths per 1000 person-years ; 95 % confidence interval ( CI ) 28.1 , 34.7 ) and the age group 60–64 displayed the highest crude mortality rate ( 58.9 deaths per 1000 person-years ; 95 % CI 42.2 , 75.5 ) . Kaplan – Meier survival estimates indicated that nonelderly patients had better survival than elderly patients ( P < 0.001 ) . Adjusted Weibull analysis indicated that elderly age status was importantly associated ( adjusted hazard ratio 1.23 , 95 % CI 1.08–1.42 ) with mortality , when controlling for sex , baseline CD4 cell count and year of therapy initiation . Conclusion : As antiretroviral treatment cohorts mature , the proportion of patients who are elderly will inevitably increase . Elderly patients may require focused clinical care that extends beyond HIV treatment Objectives : Determine outcome differences between orphaned and non-orphaned children receiving antiretroviral therapy ( ART ) . Design : Retrospective review of prospect ively recorded electronic data . Setting : Nine HIV clinics in western Kenya . Population : 279 children on ART enrolled between August 2002 and February 2005 . Main Measures : Orphan status , CD4 % , sex- and age-adjusted height ( HAZ ) and weight ( WAZ ) z scores , ART adherence , mortality . Results : Median follow-up was 34 months . Cohort included 51 % males and 54 % orphans . At ART initiation ( baseline ) , 71 % of children had CDC clinical stage B or C disease . Median CD4 % was 9 % and increased dramatically the first 30 weeks of therapy , then leveled off . Parents and guardians reported perfect adherence at every visit for 75 % of children . Adherence and orphan status were not significantly associated with CD4 % response . Adjusted for baseline age , follow-up was significantly shorter among orphaned children ( median 33 vs. 41 weeks , P = 0.096 ) . One-year mortality was 7.1 % for orphaned and 6.6 % for non-orphaned children ( P = 0.836 ) . HAZ and WAZ were significantly below norm in both groups . With ART , HAZ remained stable , while WAZ tended to increase toward the norm , especially among non-orphans . Orphans showed identical weight gains as non-orphans the first 70 weeks after start of ART but experienced reductions afterwards . Conclusions : Good ART adherence is possible in western rural Kenya . ART for HIV-infected children produced substantial and sustainable CD4 % improvement . Orphan status was not associated with worse short-term outcomes but may be a factor for long-term therapy response . ART alone may not be sufficient to reverse significant developmental lags in the HIV-positive pediatric population Adherence to combination antiretroviral therapy ( ART ) has been shown to be a determining factor in controlling viral replication , maintaining immunologic function and long-term survival in HIV-positive individuals . Little information is available on strategies to improve adherence in pediatric HIV-infected patients . We conducted a r and omized , nonblinded , pilot study to determine if a home-based nursing intervention would improve medication adherence . The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children 's Medical Center 's ( CCMC ) Pediatric and Youth HIV Program . Sixty-seven percent ( 37/55 ) of the patients and their caretakers participated . We r and omized participants to either st and ard of care or the intervention trial . The intervention was design ed to improve knowledge and underst and ing of HIV infection and HIV medications and to resolve or modify barriers to adherence . Both groups completed pre- and post-intervention question naires , assessing their knowledge and underst and ing of HIV , ART , and adherence . Adherence was estimated objective ly from medication refill history and subjectively from a self-report score . We also inferred adherence from pre- to post-test plasma viral load and CD4 + T-cell percentages . The knowledge score ( p = 0.02 ) and medication refill history ( p = 0.002 ) improved significantly in the intervention group . The adherence self-report score improved , although not significantly ( p = 0.07 ) . We did not observe statistical differences in CD4 + T-cell counts or viral load between groups . We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens |
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